Systems and methods to place one or more leads in tissue for providing functional and/or therapeutic stimulation

ABSTRACT

Systems and methods make possible the placement of one or more electrode leads in a tissue region for providing functional and/or therapeutic stimulation to tissue. The systems and methods are adapted to provide the relief of pain.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/522,918, filed Oct. 24, 2014, and entitled “Systems and Methods toPlace One or More Leads in Tissue for Providing Functional and/orTherapeutic Stimulation,” which is a continuation-in-part of U.S. patentapplication Ser. No. 12/653,029, filed Dec. 7, 2009, and entitled“Systems and Methods to Place One or More Leads in Tissue for ProvidingFunctional and/or Therapeutic Stimulation,” which claims the benefit ofU.S. Provisional Patent Application Ser. No. 61/201,030, filed Dec. 5,2008, and entitled “Systems and Methods to Place One or More Leads inTissue for Providing Functional and/or Therapeutic Stimulation,” whichare all incorporated herein by reference. In addition, U.S. patentapplication Ser. No. 14/522,918 is also a continuation in part of U.S.patent application Ser. No. 12/653,023, now U.S. Pat. No. 8,954,153,filed Dec. 7, 2009, and entitled “Systems and Methods to Place One orMore Leads in Tissue for Providing Functional and/or TherapeuticStimulation,” which claims the benefit of U.S. Provisional PatentApplication Ser. No. 61/201,030, filed Dec. 5, 2008, and entitled“Systems and Methods to Place One or More Leads in Tissue for ProvidingFunctional and/or Therapeutic Stimulation,” which are all incorporatedherein by reference.

FIELD OF INVENTION

This invention relates to systems and methods for placing one or moreelectrode leads in tissue for providing electrical stimulation totissue.

BACKGROUND OF THE INVENTION

Neurostimulation, i.e., neuromuscular stimulation (the electricalexcitation of nerves and/or muscle to directly elicit the contraction ofmuscles) and neuromodulation stimulation (the electrical excitation ofnerves, often afferent nerves, to indirectly affect the stability orperformance of a physiological system) and brain stimulation (thestimulation of cerebral or other central nervous system tissue) canprovide functional and/or therapeutic outcomes. While existing systemsand methods can provide remarkable benefits to individuals requiringneurostimulation, many quality of life issues still remain. For example,existing systems include complicated procedures to place electrodes andpulse generators, and issues remain with the migration of electrodeswhich eventually reduce the effectiveness of the neurostimulation.Furthermore, these systems are, by today's standards, relatively largeand awkward to manipulate, transport, and adhere to the patient.

There exist both external and implantable devices for providingneurostimulation in diverse therapeutic and functional restorationindications. These neuro-stimulators are able to provide treatmentand/or therapy to individual portions of the body. The operation ofthese devices typically includes the use of an electrode placed eitheron the external surface of the skin and/or a surgically implantedelectrode. In the case of external neurostimulators, surfaceelectrode(s) and/or percutaneous lead(s) having one or more electrodesmay be used to deliver electrical stimulation to the select portion ofthe patient's body.

One example of an indication where therapeutic treatment may be providedis for the treatment of pain, such as to provide a therapy to reducepain in individuals with amputated limbs. Amputation leads to chronicpain in almost all (95%) patients, regardless of how much time hadpassed since the amputation (Ephraim et al. 2005). The pain can beextremely bothersome to amputees, significantly decrease their qualityof life, correlate with increased risk of depression, and negativelyaffect their inter-personal relationships and their ability to return towork (Kashani et al 1983; Blazer et al. 1994; Cansever et al. 2003). Thepresent methods of treatment, which are primarily medications, areunsatisfactory in reducing amputation-related pain, have unwanted sideeffects, offer a low success rate, and often lead to addiction.

Most amputees have two types of pain: residual limb (stump) pain andphantom pain. Approximately 72-85% of amputees have phantom pain and68-76% of amputees have residual limb (stump) pain (Sherman and Sherman1983; Sherman et al. 1984; Ehde et al. 2000; Ephraim et al. 2005). Bothstump pain and phantom limb pain are chronic pains experienced after anamputation, and they are easily distinguished by the perceived locationof the pain. Stump pain is sensed in the portion of the limb thatremains after amputation, and phantom limb pain is perceived in theportion of the limb that has been removed. Typically, amputee patientswith severe stump pain also have severe phantom limb pain, but it isrecommended that their responses to treatment be measured independently(Jensen et al. 1985; Kooijman et al. 2000). Stump and phantom pain canbe severe and debilitating to a large proportion of persons withamputations, who will unfortunately often progress through a battery ofmanagement techniques and procedures without finding relief from theirpain (Bonica 1953; Sherman et al. 1980; Ehde et al. 2000; Loeser 2001a;Ephraim et al. 2005).

An estimated 80-95% of 1.7 millions persons who currently live withamputations plus the additional 185,000 persons expected to undergoamputation each year in the United States will suffer from stump and/orphantom pain at an annual direct cost of $1.4-2.7 billion and overallassociated costs of $13 billion (Sherman and Sherman 1983; Sherman etal. 1984; Ehde et al. 2000; Mekhail et al. 2004; Ephraim et al. 2005).Severe post-amputation pain often leads to further disability, reducedquality of life, and frequently interferes with the simple activities ofdaily life more than the amputation itself (Millstein et al. 1985;Schoppen et al. 2001; Marshall et al. 2002; Whyte and Carroll 2002; Rudyet al. 2003), and no available therapy is sufficient to manage it(Sherman et al. 1980; Jahangiri et al. 1994; Rosenquist and Haider2008).

Many techniques have been developed to treat post-amputation pain, butall of them are ultimately insufficient (Jahangiri et al. 1994). Areview in 1980 found that none of the 68 treatments available forpost-amputation pain were uniformly successful (Sherman et al. 1980),and more recent reviews have found that little has changed and thereremains a large need for an effective method of treating stump andphantom pain (Davis 1993; Wall et al. 1994; Loeser 2001a; Halbert et al.2002; Rosenquist and Haider 2008). Some studies report that as few as 1%of amputees with severe phantom and stump pain receive lasting benefitfrom any of the available treatments (Sherman and Sherman 1983; Shermanet al. 1984). Presently, most patients are managed with medications, butapproximately a third of amputees still report severe (intensity of 7-10on a scale of 0-10) phantom and stump pain.

Non-narcotic analgesics, such as acetaminophen or non-steroidalanti-inflammatory drugs (NSAIDS), have relatively minor side effects andare commonly used for several types of pain. However, they are notspecific to stump or phantom pain and are rarely sufficient in managingmoderate to severe chronic post-amputation pain (Sherman et al. 1980;Loeser 2001a; Rosenquist and Haider 2008).

The use of narcotic analgesics, such as N-methyl-D-aspartate (NDMA)antagonists, has shown only minor success with inconsistent results.Narcotics carry the risk of addiction and side effects, such as nausea,confusion, vomiting, hallucinations, drowsiness, dizziness, headache,agitation, and insomnia. Several trials of multiple narcotic agents havefailed to show statistically significant improvement in phantom pain(Stangl and Loeser 1997; Nikolajsen et al. 2000; Loeser 2001a; Maier etal. 2003; Hayes et al. 2004; Wiech et al. 2004; Rosenquist and Haider2008).

Physical methods such as adjusting the prosthesis may be helpful, butonly if the pain is due to poor prosthetic fit. Other physicaltreatments, including acupuncture, massage, and percussion orheating/cooling of the stump, have few complications but also havelimited data to support their use and have not been well acceptedclinically (Russell and Spalding 1950; Gillis 1964; Monga and Jaksic1981; Loeser 2001a).

Psychological strategies, such as biofeedback and psychotherapy, may beused as an adjunct to other therapies but are seldom sufficient, andthere are few studies demonstrating efficacy and these approaches arenot specific to stump or phantom pain (Dougherty 1980; Sherman 1980).Mirror-box therapy has demonstrated mixed results and is not widely usedin clinical practice (Ramachandran and Rogers-Ramachandran 1996; Brodieet al. 2007; Chan et al. 2007; Rosenquist and Haider 2008).

Many surgical procedures have been attempted, but few are successful andmost are contraindicated for the majority of the amputee patients(Loeser 2001a). Because neuromas are implicated with stump and phantompain, there have been many attempts to remove them surgically, butultimately a new neuroma will develop each time a nerve is cut and thepain relief only lasts for the 3 weeks that it takes for a new neuromato form (Sturm 1975; Sunderland 1978; Sherman 1980). Furthermore,neuroablative procedures carry the risk of producing deafferentationpain, and any surgical procedure has a greater chance of failure thansuccess (Loser 2001a; Rosenquist and Haider 2008). Thus, present medicaltreatments of stump and phantom pain are inadequate, and most sufferersresort to living with pain that is poorly controlled with medications.

Electrical stimulation systems hold promise for relief ofpost-amputation pain, but widespread use of available systems islimited.

Transcutaneous electrical nerve stimulation (TENS) has been cleared bythe FDA for treatment of pain and may be successful in reducingpost-amputation pain. TENS systems are external neurostimulation devicesthat use electrodes placed on the skin surface to activate target nervesbelow the skin surface. TENS has a low rate of serious complications,but it also has a relatively low (i.e., less than 25%) long-term rate ofsuccess.

Application of transcutaneous electrical nerve stimulation (TENS) hasbeen used to treat stump and phantom pain successfully, but it has lowlong-term patient compliance, because it may cause additional discomfortby generating cutaneous pain signals due to the electrical stimulationbeing applied through the skin, and the overall system is bulky,cumbersome, and not suited for long-term use (Nashold and Goldner 1975;Sherman 1980; Finsen et al. 1988).

Spinal cord stimulation (SCS) systems are FDA approved as implantableneurostimulation devices marketed in the United States for treatment ofpain. Similar to TENS, when SCS evokes paresthesias that cover theregion of pain, it confirms that the location of the electrode and thestimulus intensity should be sufficient to provide pain relief and painrelief can be excellent initially, but maintaining sufficientparesthesia coverage is often a problem as the lead migrates along thespinal canal (Krainick et al. 1980; Sharan et al. 2002; Buchser andThomson 2003).

Lead migration is the most common complication for spinal cordstimulators occurring in up to 45-88% of the cases (North et al. 1991;Andersen 1997; Spincemaille et al. 2000; Sharan et al. 2002). When thelead migrates, the active contact moves farther from the target fibersand loses the ability to generate paresthesias in the target area. SCSsystems attempt to address this problem by using leads with multiplecontacts so that as the lead travels, the next contact in line can beselected to be the active contact.

Spinal cord stimulation is limited by the invasive procedure and thedecrease in efficacy as the lead migrates. When it can produceparesthesias in the region of pain, spinal cord stimulation is typicallysuccessful initially in reducing stump and phantom pain, but over timethe paresthesia coverage and pain reduction is often lost as the leadmigrates away from its target (North et al. 1991; Andersen 1997; Loeser2001a).

Brain stimulation systems are limited by the lack of patient selectioncriteria and the lack of studies demonstrating long-term efficacy.

Peripheral nerve stimulation may be effective in reducingpost-amputation pain, but it previously required specialized surgeons toplace cuff- or paddle-style leads around the nerves in a time consumingprocedure.

Immediately following amputation, all patients experience short-term(postoperative) pain, but it usually resolves within a month as thewound heals. In contrast, a long-term pain often develops and persistsin the stump and phantom limb after the amputated limb has healed into ahealthy stump. Stump and phantom pain are thought to have a peripheraland central component, and both components may be mediated bystimulating the peripheral nerves that were transected duringamputation.

Neuromas develop when a peripheral nerve is cut and the proximal portionproduces new axon growth that forms a tangled mass as it fails toconnect with the missing distal portion of the nerve. All amputationsproduce neuromas and not all neuromas are painful, but neuromas arethought to be a major source of pain after amputation (Burchiel andRussell 1987; Loeser 2001a; Rosenquist and Haider 2008). Neuromas maygenerate spontaneous activity (Wall and Gutnick 1974), and the level ofactivity in afferent fibers innervating the region of pain has beenlinked to the level of post-amputation pain (Nystrom and Hagbarth 1981).

As previously described, electrical stimulation has been used and shownto be effective in treating amputee pain, but present methods ofimplementation have practical limitations that prevent widespread use.External systems are too cumbersome, and implanted spinal cordstimulation systems often have problems of lead migration along thespinal canal, resulting in either the need for frequent reprogramming orclinical failure.

It is time that systems and methods for providing neurostimulationaddress not only specific prosthetic or therapeutic objections, but alsoaddress the quality of life of the individual requiringneurostimulation, including a need to treat amputee pain withminimally-invasive systems and methods that may not requirereprogramming, and include lead(s) that can be inserted percutaneouslynear target peripheral nerve(s) and resist(s) migration.

The electrical stimulation of nerves, often afferent nerves, toindirectly affect the stability or performance of a physiological systemcan provide functional and/or therapeutic outcomes, and has been usedfor activating target nerves to provide therapeutic relief of pain.

While existing systems and methods can provide remarkable benefits toindividuals requiring therapeutic relief, many issues and the need forimprovements still remain.

Many techniques have been developed to treat pain, but all of them areultimately insufficient.

Non-narcotic analgesics, such as acetaminophen or non-steroidalanti-inflammatory drugs (NSAIDS), have relatively minor side effects andare commonly used for several types of pain. However, they are rarelysufficient in managing moderate to severe chronic pain (Sherman et al.1980; Loeser 2001a; Rosenquist and Haider 2008).

The use of narcotic analgesics, such as N-methyl-D-aspartate (NDMA)antagonists, has shown only minor success with inconsistent results.Narcotics carry the risk of addiction and side effects, such as nausea,confusion, vomiting, hallucinations, drowsiness, dizziness, headache,agitation, and insomnia.

Psychological strategies, such as biofeedback and psychotherapy, may beused as an adjunct to other therapies but are seldom sufficient, andthere are few studies demonstrating efficacy.

Electrical stimulation systems have been used for the relief of pain,but widespread use of available systems is limited.

There exist both external and implantable devices for providingelectrical stimulation to activate nerves and/or muscles to providetherapeutic relief of pain. These “neurostimulators” are able to providetreatment and/or therapy to individual portions of the body. Theoperation of these devices typically includes the use of an electrodeplaced either on the external surface of the skin and/or a surgicallyimplanted electrode. In most cases, surface electrode(s), cuff-styleelectrode(s), paddle-style electrode(s), spinal column electrodes,and/or percutaneous lead(s) having one or more electrodes may be used todeliver electrical stimulation to the select portion of the patient'sbody.

Transcutaneous electrical nerve stimulation (TENS) has been cleared bythe FDA for treatment of pain. TENS systems are externalneurostimulation devices that use electrodes placed on the skin surfaceto activate target nerves below the skin surface. TENS has a low rate ofserious complications, but it also has a relatively low (i.e., less than25%) long-term rate of success.

Application of TENS has been used to treat pain successfully, but it haslow long-term patient compliance, because it may cause additionaldiscomfort by generating cutaneous pain signals due to the electricalstimulation being applied through the skin, and the overall system isbulky, cumbersome, and not suited for long-term use (Nashold and Goldner1975; Sherman 1980; Finsen et al. 1988).

In addition, several clinical and technical issues associated withsurface electrical stimulation have prevented it from becoming a widelyaccepted treatment method. First, stimulation of cutaneous painreceptors cannot be avoided resulting in stimulation-induced pain thatlimits patient tolerance and compliance. Second, electrical stimulationis delivered at a relatively high frequency to preventstimulation-induced pain, which leads to early onset of muscle fatiguein turn preventing patients from properly using their arm. Third, it isdifficult to stimulate deep nerves and/or muscles with surfaceelectrodes without stimulating overlying, more superficial nerves and/ormuscles resulting in unwanted stimulation. Finally, clinical skill andintensive patient training is required to place surface electrodesreliably on a daily basis and adjust stimulation parameters to provideoptimal treatment. The required daily maintenance and adjustment of asurface electrical stimulation system is a major burden on both patientand caregiver.

Spinal cord stimulation (SCS) systems are FDA approved as implantableneurostimulation devices marketed in the United States for treatment ofpain. Similar to TENS, when SCS evokes paresthesias that cover theregion of pain, it confirms that the location of the electrode and thestimulus intensity should be sufficient to provide pain relief and painrelief can be excellent initially, but maintaining sufficientparesthesia coverage is often a problem as the lead migrates along thespinal canal (Krainick et al. 1980; Sharan et al. 2002; Buchser andThomson 2003).

Spinal cord stimulation is limited by the invasive procedure and thedecrease in efficacy as the lead migrates. When it can produceparesthesias in the region of pain, spinal cord stimulation is typicallysuccessful initially in reducing pain, but over time the paresthesiacoverage and pain reduction is often lost as the lead migrates away fromits target (North et al. 1991; Andersen 1997; Loeser 2001a).

Lead migration is the most common complication for spinal cordstimulators occurring in up to 45-88% of the cases (North et al. 1991;Andersen 1997; Spincemaille et al. 2000; Sharan et al. 2002). When thelead migrates, the active contact moves farther from the target fibersand loses the ability to generate paresthesias in the target area. SCSsystems attempt to address this problem by using leads with multiplecontacts so that as the lead travels, the next contact in line can beselected to be the active contact.

Peripheral nerve stimulation may be effective in reducing pain, but itpreviously required specialized surgeons to place cuff- or paddle-styleleads around the nerves in a time consuming procedure.

These methods of implementation have practical limitations that preventwidespread use. External systems are too cumbersome, and implantedspinal cord stimulation systems often have problems of lead migrationalong the spinal canal, resulting in either the need for frequentreprogramming or clinical failure.

Percutaneous, intramuscular electrical stimulation for the treatment ofpost-stroke shoulder pain has been studied as an alternative to surfaceelectrical stimulation. A feasibility study (Chae, Yu, and Walker, 2001)and a pilot study (Chae, Yu, and Walker, 2005) showed significantreduction in pain and no significant adverse events when usingpercutaneous, intramuscular electrical stimulation in shoulder muscles.

This form of percutaneous, intramuscular electrical stimulation can becharacterized as “motor point” stimulation of muscle. To relieve pain inthe target muscle, the percutaneous lead is placed in the muscle that isexperiencing the pain near the point where a motor nerve enters themuscle (i.e., the motor point). In “motor point” stimulation of muscle,the muscle experiencing pain is the same muscle in which the lead isplaced. In “motor point” stimulation of muscle, the pain is felt andrelieved in the area where the lead is located.

SUMMARY OF THE INVENTION

The invention provides improved systems and methods for placing one ormore electrode leads in tissue for providing electrical stimulation totissue to reduce pain.

One aspect of the invention provides lead placement procedures that maybe used for placing a single electrode lead to activate a target nerveand/or nerves and/or nerve bundles (e.g., the brachial plexus, sciaticnerve, and/or femoral nerve, and/or their roots or branches) that carrythe pain signal(s) in a system for the relief of neuropathic pain, suchas post-amputation pain, but is not exclusive to this application. Forexample, if the pinky finger hurts, the systems and methods are welladapted to stimulate the ulnar nerve (which innervates the pinkyfinger). The procedures optimally allow using only a single lead,although it is to be appreciated that more than one lead(s) may be used,to activate a greater range of target nerves and/or nerve bundles.

Other features and advantages of the inventions are set forth in thefollowing specification and attached drawings.

The invention provides systems and methods for placing one or more leadsin tissue for providing electrical stimulation to tissue to treat painin a manner unlike prior systems and methods.

The invention provides systems and methods incorporate a discovery thatpain felt in a given region of the body can be treated, not by motorpoint stimulation of muscle in the local region where pain is felt, butby stimulating muscle close to a “nerve of passage” in a region that issuperior (i.e., cranial or upstream toward the spinal column) to theregion where pain is felt. Neural impulses comprising pain felt in agiven muscle or cutaneous region of the body pass through spinal nervesthat arise from one or more nerve plexuses. The spinal nerves in a nerveplexus, which comprise trunks that divide by divisions and/or cords intobranches, comprise “nerves of passage.” It has been discovered thatapplying stimulation in a muscle near a targeted nerve of passagerelieves pain that manifests itself in a region that is inferior (i.e.,caudal or downstream from the spinal column) from where stimulation isactually applied.

Phantom (or amputee) pain is one example of the effectiveness of “nervesof passage” stimulation, because the area in which phantom pain is feltdoes not physically exist. A lead cannot be physically placed in themuscles that hurt, because those muscles were amputated. Still, byapplying stimulation in a muscle that has not been amputated near atargeted nerve of passage that, before amputation, natively innervatedthe amputated muscles, phantom pain can be treated.

Chronic or acute pain in existing, non-amputated muscles can also betreated by “nerves of passage” stimulation. By applying stimulation inan existing muscle near a targeted nerve of passage that caudallyinnervates the region where chronic or acute pain is manifested, thepain can be treated.

In “nerves of passage” stimulation, a lead can be placed in a musclethat is conveniently located near a nerve trunk that passes by the leadon the way to the painful area. On “nerves of passage” stimulation, thelead is placed in a muscle that is not the target (painful) muscle, butrather a muscle that is upstream from the painful region, because theproximal muscle presents a convenient and useful location to place thelead.

The systems and methods make possible the treatment of chronic or acutepain in which muscle contraction cannot be evoked (e.g. in the case ofamputation pain in which the target area has been amputated is no longerphysically present), or other cases of nerve damage either due to adegenerative diseases or condition such as diabetes of impaired vascularfunction (in which the nerves are slowly degenerating, progressing fromthe periphery), or due to trauma. The systems and methods make possiblethe placement stimulation leads in regions distant from the motor pointor region of pain, e.g., where easier access or more reliable access ora clinician-preferred access be accomplished; or in situations where themotor nerve point is not available, damaged, traumatized, or otherwisenot desirable; or in situations where it is desirable to stimulate morethan one motor point with a single lead; or for cosmetic reasons; or toshorten the distance between the lead and its connection with a pulsegenerator; or to avoid tunneling over a large area.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an anatomical view of a patient utilizing one embodiment ofthe present invention, including a percutaneous electrode lead coupledto an external pulse generator.

FIG. 2 is an anatomical view of a patient utilizing another embodimentof the present invention, including an implanted electrode lead coupledto an implanted pulse generator.

FIGS. 3A and 3B are anatomical views of a patient's shoulder showing theanatomical landmarks useful to guide the placement of a needle electrodeas a component and/or step of the present invention.

FIG. 4 is an anatomical view of the shoulder as shown in FIG. 3B,showing infraclavicular and subcoracoid neuroanatomy with a needleintroducer depicting a direction of lead insertion toward the brachialplexus.

FIG. 5 is an anatomical view similar to FIG. 4, except showing greaterdetail of the brachial plexus and the lead insertion, and showing ananticipated region of activation.

FIG. 6 is an anatomical cross-sectional view (perpendicular to the axisof the lead insertion) of the brachial plexus and surrounding tissue.

FIG. 7 is an anatomical view of the shoulder as shown in FIG. 3B,showing the percutaneous lead inserted through the skin in the targetarea in the shoulder via an introducer needle.

FIG. 8 is an anatomical view of the shoulder as shown in FIG. 7, showingthe percutaneous lead coupled to the external pulse generator and thereturn electrode.

FIG. 9 is a view of a possible electrode lead for use with the systemsand methods of the present invention.

FIGS. 10 and 11 are perspective views of another possible electrode leadfor use with the systems and methods of the present invention, the leadincluding anchoring members.

FIG. 12 is a plan view of a kit packaging the systems and methodscomponents for use, along with instructions for use.

FIG. 13 is a plan view of an additional kit packaging the systems andmethods components for use, along with instructions for use.

FIGS. 14A and 14B are schematic anatomic views, respectively anteriorand lateral, of a human peripheral nervous system.

FIG. 15A is a schematic anatomic view of a human spine, showing thevarious regions and the vertebrae comprising the regions.

FIGS. 15B and 15C are schematic anatomic views of the dermatomeboundaries of a human.

FIGS. 16A, 16B, and 16C are anatomic views of the intercostal spinalnerves of a human.

FIGS. 17A and 17B are anatomic views of the spinal nerves of thebrachial plexus.

FIG. 18 is an anatomic views of the spinal nerves of the lumbar plexus.

FIG. 19 is an anatomic view of the spinal nerves of the sacral plexus.

FIG. 20 is an anatomic view of the spinal nerves of the cervical plexus.

FIG. 21 is an anatomic view of the spinal nerves of the solar plexus.

FIG. 22 is an idealized, diagrammatic view showing a motor pointstimulation system.

FIG. 23 is an idealized, diagrammatic view showing a nerve of passagestimulation system.

FIGS. 24A to 24D are views showing a percutaneous lead that can form apart of a nerve of passage stimulation system.

FIG. 25 is a view of a package containing a nerve of passage stimulationsystem.

FIGS. 26A/B and 27A/B are representative leads that can form a part of anerve of passage stimulation system.

FIGS. 28A and 28B are schematic anatomic views of a system for applyingnerve of passage stimulation to spinal nerves in the brachial plexus.

FIGS. 29A, 29B, and 29C are schematic anatomic views of a system forapplying nerve of passage stimulation to a femoral nerve.

FIGS. 30A, 30B, and 30C are schematic anatomic views of a system forapplying nerve of passage stimulation to a sciatic/tibial nerve.

FIGS. 31A and 31B are schematic sectional anatomic views of systems forapplying nerve of passage stimulation to a femoral nerve and asciatic/tibial nerve.

FIGS. 32A, 32B, and 32C are schematic sectional anatomic views of asystem for applying nerve of passage stimulation along a sciatic/tibialnerve.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Although the disclosure hereof is detailed and exact to enable thoseskilled in the art to practice the invention, the physical embodimentsherein disclosed merely exemplify the invention which may be embodied inother specific structures. While the desired embodiment has beendescribed, the details may be changed without departing from theinvention.

Any elements described herein as singular can be pluralized (i.e.,anything described as “one” can be more than one). Any species elementof a genus element can have the characteristics or elements of any otherspecies element of that genus. The described configurations, elements orcomplete assemblies and methods and their elements for carrying out theinvention, and variations of aspects of the invention can be combinedand modified with, each other in any combination.

The various aspects of the invention will be described in connectionwith the placement of one or more leads 12 having one or more electrodes14, in tissue, e.g., on, in, or near nerves and/or muscles, for improvedrecruitment of targeted nerves or muscles for prosthetic or therapeuticpurposes, such as for the treatment of post-amputation pain. That isbecause the features and advantages that arise due to the invention arewell suited to this purpose. Still, it should be appreciated that thevarious aspects of the invention can be applied to achieve otherobjectives as well.

I. REDUCTION OF POST-AMPUTATION PAIN

The present novel invention provides systems and methods for thereduction of pain. Most amputees have two types of pain: residual limb(stump) pain and phantom pain. The systems and methods of the presentinvention are adapted to reduce either and/or both types of pain bystimulating target nerves, generally on the same side of the body as theamputation, i.e., the nerves that innervate the regions of pain. It isto be appreciated that amputation can include any or all portions of alimb, including arms and legs in both humans and animals.

The present novel invention provides systems and methods that placepercutaneous electrode lead(s) 12 appropriately in patients withamputations to electrically activate a target nerve and/or nerves and/ornerve bundles (e.g., the brachial plexus, sciatic nerve, and/or femoralnerve, and/or their roots or branches) that carry the pain signal(s).For example, if the pinky finger hurts, the systems and methods are welladapted to stimulate the ulnar nerve (which innervates the pinkyfinger). If electrical stimulation activates the target nervesufficiently at the correct intensity, then the patient will feel acomfortable tingling sensation called a paresthesia in the same regionas their pain. It is to be appreciated that the sensation could bedescribed with other words such as buzzing, thumping, etc. Just as thepatient can have pain in the stump and/or the phantom limb, electricalstimulation can evoke paresthesias that the patient also feels in thestump and/or phantom limb. Evoking paresthesias in the regions of painconfirms correct lead placement and indicates stimulus intensity issufficient to reduce pain.

The ability to insert the lead 12 percutaneously near a targetperipheral nerve simplifies the approach to a quick (e.g., 5, or 10, or20 minute) procedure, such as an out-patient procedure that can beperformed in a standard community-based clinic, allowing widespread useand providing a minimally-invasive screening test to determine ifpatients will benefit from the systems and methods of the presentinvention, including a percutaneous system 10 and/or a fully implantedsystem 11 (see FIGS. 1 and 2).

The systems and methods of the present invention are well suited toplace a percutaneous lead 12 on, in, or near the brachial plexus with aquick procedure to generate electrically a comfortable (tingling)sensation of paresthesia in the regions of stump and phantom pain andreduce the patients' pain.

In a percutaneous system 10, the lead 12 may be percutaneously placednear the brachial plexus and exit at the skin puncture site 16 andcoupled to an external pulse generator 26. The percutaneously placedlead 12 and external pulse generator 26 may provide a screening testfunction to confirm paresthesia coverage and/or pain relief of thepainful areas. If the screening test is successful, the patient mayproceed to a home-trial (e.g., a day, week, month, year) to determine ifpain relief can be sustained in the home environment. If either thescreening test or home trial is unsuccessful, the lead 12 may be quicklyand easily removed. It is to be appreciated that a home-trial is not arequirement for either the percutaneous system or a fully implantedsystem.

However, if the screening test and/or home-trial are successful, thepatient's percutaneous system may be converted into a fully implantedsystem 11 by replacing the external pulse generator 26 with animplantable pulse generator 28 that is implanted in a convenient area(e.g., the subclavicular area), and coupling a new sterile lead 12, or asterile lead extension, to the implantable pule generator 28.

Inserting the lead 12 percutaneously allows the lead 12 to be placedquickly and easily, and placing the lead 12 in a peripheral location,where it is less likely to be dislodged, addresses the lead migrationproblems of spinal cord stimulation that result in decreased paresthesiacoverage, decreased pain relief, and the need for frequent patientvisits for reprogramming.

In the exemplary embodiment of the present invention, placing thepercutaneous lead 12 in adipose tissue of the infraclavicular andsubcoracoid space near the brachial plexus (to be described in greaterdetail below), may minimize complications related to lead movement.Perineural catheters connected to infusion pumps have been placed insimilar locations for use by ambulatory patients in their homeenvironment and have a low rate of catheter dislocations andcomplications (Wilson et al 1998; Ekatodramis and Borgeat 2000; Ilfeldet al. 2002).

In the percutaneous system 10, an electrode lead 12, such as a coiledfine wire electrode lead may be used because it is minimally-invasiveand previous studies suggest it will perform well in this location andtissue type during use.

In the fully implanted system 11, the same or different electrode lead12 may be used, such as a slightly larger electrode lead that may besized and configured to withstand greater mechanical forces and resistmigration during long-term use. A larger electrode lead 12 may be sizedand configured to withstand forces in excess of those anticipated nearthe brachial plexus, and other similarly flexible regions of the body.

II. IMPLANTING THE ELECTRODE LEAD

A. The Anatomic Landmarks

As already described, certain components of the systems and methods ofthe present invention are well adapted to be implanted in a particularlocation near the patient's shoulder, where it has been discovered thateffective stimulation of the nerves of the brachial plexus can beachieved with a single electrode lead 12 to reduce pain. As can be seenin FIGS. 3A and 3B, the main anatomic landmarks guiding the uniqueplacement of these components are the clavicle and the coracoid process.

FIG. 4 shows the clavicle as a doubly curved short bone that connectsthe arm (upper limb) to the body (trunk), located directly above thefirst rib. It acts as a shunt to keep the scapula in position so the armcan hang freely. The coracoid process is a small finger-like structureon the upper lateral corner of the scapula. Pointing laterally forward,it, together with the acromion, serves to stabilize the shoulder joint.It is palpable in the deltopectoral groove between the deltoid andpectoralis major muscles.

Guided by these landmarks, the brachial plexus can be identified.Referring to FIGS. 4 and 5, the brachial plexus comprises an arrangementof nerve fibers, running from the spine, formed by the ventral rami ofthe lower cervical and upper thoracic nerve roots, specifically fromabove the fifth cervical vertebra to underneath the first thoracicvertebra (C5-T1). It proceeds through the neck, under the clavicle andgenerally anterior to the scapula, through the armpit region and intothe arm. The brachial plexus is generally responsible for cutaneous andmuscular innervation of the entire upper limb, with only two exceptions;the trapezius muscle is innervated by the spinal accessory nerve and anarea of skin near the armpit is innervated by the intercostobrachialisnerve.

FIG. 6 is a cross-sectional view (perpendicular to the axis of the leadinsertion) of the brachial plexus and surrounding tissue (Moayeri et al.2008). As can be seen in FIG. 6, the brachial plexus is surrounded by alarge amount of adipose tissue 54 in the infraclavicular and subcoracoidregions, where the electrode lead 12 will be placed, and is well suitedfor use in adipose tissue. In the infraclavicular and subcoracoidsections of cadavers studied, the brachial plexus was surrounded byabout 6.90±1.82 cm² to about 7.06±1.48 cm², which is ample area to placethe electrode lead 12.

B. Implantation Methodology

Representative lead insertion techniques will now be described to placean electrode lead 12 in a desired location in adipose tissue 54 at ornear the brachial plexus. It is this desired placement that makespossible the stimulation of the brachial plexus with a single lead 12 toprovide pain relief.

FIGS. 7 and 8 show representative embodiments of the steps thatrepresentative instructions for use 58 can incorporate or direct for theplacement of an electrode lead 12 in a targeted tissue region for therelief of pain, such as post-amputation pain. The instructions mayinclude a series of steps that can be followed to carry out portion orportions of the procedure. These steps may include, but are not limitedto:

1) Place the patient in a supine position with head turned away from thelead insertion site 16 and forearm laid to rest in a neutral positionbeside the body.

2) Prepare the lead insertion site with antiseptic and localsubcutaneous anesthetic (e.g., 2% lidocaine).

3) Locate the site of skin puncture 16 with landmarks as necessary, suchas those previously described, e.g., approximately 2 cm medial andcaudal to the coracoid process.

4) Insert a sterile percutaneous electrode lead 12 at a predeterminedangle based on landmarks used, e.g., approximately 45 degrees towardsthe top of the axillary fossa in relation to the axillary artery. Thelead 12 may be preloaded in the introducer needle 30 (see FIG. 7).

5) Place a surface stimulation return electrode 24 in proximity of thearea in which the percutaneous lead 12 has been placed. Test stimulationwill be applied to the lead 12, with the surface electrode 24 providinga return path. The surface electrode 24 may be placed adjacent to thelead. Its position is not critical to the therapy and it can be movedthroughout the therapy to reduce the risk of skin irritation.

6) Couple the lead 12 to the external pulse generator 26 and to thereturn electrode 24 (see FIG. 8). Set the desired stimulationparameters. Test stimulation may be delivered using a current-regulatedpulse generator, for example. The external pulse generator 26 may beprogrammed to 4 mA, 100 μs, 100 Hz, and an on-off duty cycle of 0.25sec., as a non-limiting example.

7) Advance the introducer slowly until the subject reports the firstevoked sensation in the stump or phantom upper limb (e.g., hand).Progressively reduce the stimulus amplitude and advance the introducermore slowly until the sensation can be evoked in the phantom upper limbat a predetermined stimulus amplitude (e.g., 1 mA). Stop the advancementof the introducer, and increase the stimulus amplitude in smallincrements (e.g., 0.1 mA) until the stimulation-evoked tinglingsensation (paresthesia) expands to overlay the entire region of pain inthe subject's stump and phantom limb.

It is expected to locate the brachial plexus after inserting theintroducer approximately 4 cm from the site of skin puncture 16. At thisdepth, it is expected that a low stimulus intensity may evokecomfortable sensations (paresthesia) without generating musclecontraction (Nashold and Goldner 1975; Picaza et al. 1975; Nashold etal. 1982).

8) Withdraw the introducer 30, leaving the percutaneous lead 12 inproximity to the brachial plexus.

9) Cover the percutaneous exit site and lead 12 with a bandage 32. Abandage 34 may also be used to secure the external portion of the lead12 (or an extension cable used to couple the lead 12 to the externalpulse generator) to the skin (see FIG. 1). It is expected the length oftime to place the lead 12 to be less than 10 minutes, although theprocess may be shorter or longer.

10) Vary the stimulus amplitude in small steps (e.g., 0.1-0.5 mA) todetermine the thresholds at which stimulation evokes first sensation(T_(SEN)), sensation (paresthesia) superimposed on the region of pain(T_(SUP)), muscle twitch (T_(MUS)) of the triceps brachii (innervated bythe radial nerve branch of the brachial plexus), and maximum comfortablesensation (T_(MAX)). Query the subject at each stimulus amplitude todetermine sensation level, and visually monitor muscle response. Recordthe results.

11) It is possible that stimulation intensity may need to be increasedslightly during the process due to causes such as habituation or thesubject becoming accustomed to sensation, but the need for increasedintensity is unlikely and usually only occurs after several days toweeks to months as the tissue encapsulates and the subject accommodatesto stimulation (Nashold 1975; Krainick and Thoden 1981; Goldman et al.2008). It is to be appreciated that the need for increased intensitycould happen at any time, even years out, which would likely be due toeither lead migration or habituation, but may also be due reasonsranging from nerve damage to plasticity/reorganization in the centralnervous system.

12) If paresthesias cannot be evoked with the initial lead placement,redirect the introducer 30 either caudal or cephalad, but avoid the lungby never directing the needle introducer 30 medially.

13) If sensations still cannot be evoked in a given subject, then themuscle twitch response of the triceps brachii may be used to guide leadplacement and then increase stimulus intensity until sufficientparesthesias are elicited in the stump and phantom limb. Minimal musclecontraction may be acceptable if it is well tolerated by the amputeepatient in exchange for significant pain relief and if it does not leadto additional discomfort or fatigue (Long 1973).

14) If stimulation evokes muscle contraction at a lower stimulusthreshold than paresthesia (e.g. if T_(MUS)≦T_(SUP)) and contractionleads to discomfort, then a lower stimulus frequency (e.g., 12 Hz) maybe used because low frequencies (e.g., 4-20 Hz) have been shown tominimize discomfort due to muscle contraction and provide >50% relief ofshoulder pain in stroke patients while still inhibiting transmission ofpain signals in the central nervous system in animals (Chung et al.1984; Yu et al. 2001, 2004; Chae et al. 2005). If continued musclecontraction leads to pain due to fatigue, change the duty cycle, usingparameters shown to reduce muscle fatigue and related discomfort in theupper extremity (e.g. 5 s ramp up, 10 s on, 5 s ramp down, 10 s off) (Yuet al. 2004; Chae et al. 2005).

15) If stimulation fails to elicit paresthesia in all areas of pain,then a second percutaneous lead 12′ (not shown) may need to be placed tostimulate the nerves that are not activated by the first lead 12. Ifparesthesia coverage is incomplete, it may likely be due to insufficientactivation of the musculocutaneous nerve because it has the mostproximal branch point relative to the other nerves and is the mostlikely to be missed during single-injection nerve blocks of the brachialplexus. To place a lead near the musculocutaneous nerve, use themodified coracoid approach (a double-stimulation technique) that targetsthe musculocutaneous nerve in addition to the main trunk of the brachialplexus, as described above (Desroches 2003; Minville et al. 2005).

16) If stimulation is successful, i.e., if the screening test and/orhome-trial are successful, the patient's percutaneous system 10 (seeFIG. 1) may be converted into a fully implanted system 11 by replacingthe external pulse generator 26 with an implantable pulse generator 28that is implanted in a convenient area (e.g., the subclavicular area).In one embodiment, the electrode lead 12 used in the screening testand/or home-trial may be totally removed and discarded, and a newcompletely implantable lead may be tunneled subcutaneously and coupledto the implantable pulse generator. In an alternative embodiment, a twopart lead may be incorporated in the screening test and/or home-trialwhere the implantable part is completely under the skin and connected toa percutaneous connector (i.e., extension) that can be discarded afterremoval. The implantable part may then be tunneled and coupled to theimplantable pulse generator, or a new sterile extension may be used tocouple the lead to the implantable pulse generator.

III. ELECTRODE LEAD CONFIGURATIONS

It is to be appreciated that the configuration of one or more leads 12and electrodes 14, and the manner in which they are implanted can vary.Stimulation may be applied through an electrode lead 12, such as a finewire electrode, paddle electrode, intramuscular electrode, orgeneral-purpose electrode, inserted via a needle introducer orsurgically implanted in proximity of the target site. Once properplacement is confirmed, the needle may be withdrawn, leaving theelectrode in place. Stimulation may also be applied through apenetrating electrode, such as an electrode array comprised of anynumber (i.e., one or more) of needle-like electrodes that are insertedinto the target site. In both cases, the lead may placed using aneedle-like introducer, allowing the lead/electrode placement to beminimally invasive.

The electrode 14 may be electrically insulated everywhere except at one(monopolar), or two (bipolar), or three (tripolar), for example,conduction locations near its distal tip. Each of the conductionlocations may be connected to one or more conductors that run the lengthof the electrode and lead 12, proving electrical continuity from theconduction location through the lead 12 to the stimulator 26 or 28.

The electrode lead 12 is desirably provided in a sterile package, andmay be pre-loaded in the introducer needle 30. The lead 12 desirablypossess mechanical properties in terms of flexibility and fatigue lifethat provide an operating life free of mechanical and/or electricalfailure, taking into account the dynamics of the surrounding tissue(i.e., stretching, bending, pushing, pulling, crushing, etc.). Thematerial of the electrode desirably discourages the in-growth ofconnective tissue along its length, so as not to inhibit its withdrawalat the end of its use. However, it may be desirable to encourage thein-growth of connective tissue at the distal tip of the electrode, toenhance its anchoring in tissue.

One embodiment of the lead 12 shown in FIG. 9 may comprise a minimallyinvasive coiled fine wire lead 12 and electrode 14. The electrode 14 mayalso include, at its distal tip, an anchoring element 48. In theillustrated embodiment, the anchoring element 48 takes the form of asimple barb or bend. The anchoring element 48 is sized and configured sothat, when in contact with tissue, it takes purchase in tissue, toresist dislodgement or migration of the electrode out of the correctlocation in the surrounding tissue. Desirably, the anchoring element 48is prevented from fully engaging body tissue until after the electrode14 has been deployed. The electrode may not be deployed until after ithas been correctly located during the implantation (lead placement)process, as previously described.

An alternative embodiment of an electrode lead 12 shown in FIGS. 10 and11, may also include, at or near its distal tip or region, one or moreanchoring element(s) 70. In the illustrated embodiment, the anchoringelement 70 takes the form of an array of shovel-like paddles or scallops76 proximal to the proximal-most electrode 14 (although a paddle 76 orpaddles could also be proximal to the distal most electrode 14, or couldalso be distal to the distal most electrode 14). The paddles 76 as shownare sized and configured so they will not cut or score the surroundingtissue. The anchoring element 70 is sized and configured so that, whenin contact with tissue, it takes purchase in tissue, to resistdislodgement or migration of the electrode out of the correct locationin the surrounding tissue (e.g., soft adipose tissue 54). Desirably, theanchoring element 70 is prevented from fully engaging body tissue untilafter the electrode 14 has been deployed. The electrode is not deployeduntil after it has been correctly located during the implantation (leadplacement) process, as previously described. In addition, the lead 12may include one or more ink markings 74, 75 to aid the physician in itsproper placement.

Alternatively, or in combination, stimulation may be applied through anytype of nerve cuff (spiral, helical, cylindrical, book, flat interfacenerve electrode (FINE), slowly closing FINE, etc.) that is surgicallyplaced within muscle at the target site.

In all cases, the lead may exit through the skin and connect with one ormore external stimulators 26, or the lead(s) may be routedsubcutaneously to one or more implanted pulse generators 28, or they maybe connected as needed to internal and external coils for RF (RadioFrequency) wireless telemetry communications or an inductively coupledtelemetry to control the implanted pulse generator. The implanted pulsegenerator 28 may be located some distance (remote) from the electrode14, or an implanted pulse generator may be integrated with anelectrode(s), eliminating the need to route the lead subcutaneously tothe implanted pulse generator.

Control of the stimulator and stimulation parameters may be provided byone or more external controllers. In the case of an external stimulator,the controller may be integrated with the external stimulator. Theimplanted pulse generator external controller (i.e., clinicalprogrammer) may be a remote unit that uses RF (Radio Frequency) wirelesstelemetry communications (rather than an inductively coupled telemetry)to control the implanted pulse generator. The external or implantablepulse generator may use passive charge recovery to generate thestimulation waveform, regulated voltage (e.g., 10 mV to 20 V), and/orregulated current (e.g., about 10 pA to about 50 mA). Passive chargerecovery is one method of generating a biphasic, charge-balanced pulseas desired for tissue stimulation without severe side effects due to aDC component of the current.

The neurostimulation pulse may by monophasic, biphasic, and/ormulti-phasic. In the case of the biphasic or multi-phasic pulse, thepulse may be symmetrical or asymmetrical. Its shape may be rectangularor exponential or a combination of rectangular and exponentialwaveforms. The pulse width of each phase may range between e.g., about0.1 μsec. to about 1.0 sec., as non-limiting examples.

Pulses may be applied in continuous or intermittent trains (i.e., thestimulus frequency changes as a function of time). In the case ofintermittent pulses, the on/off duty cycle of pulses may be symmetricalor asymmetrical, and the duty cycle may be regular and repeatable fromone intermittent burst to the next or the duty cycle of each set ofbursts may vary in a random (or pseudo random) fashion. Varying thestimulus frequency and/or duty cycle may assist in warding offhabituation because of the stimulus modulation.

The stimulating frequency may range from e.g., about 1 Hz to about 300Hz, and the frequency of stimulation may be constant or varying. In thecase of applying stimulation with varying frequencies, the frequenciesmay vary in a consistent and repeatable pattern or in a random (orpseudo random) fashion or a combination of repeatable and randompatterns.

IV. SYSTEM KITS

As FIGS. 12 and 13 show, the various devices and components justdescribed can be consolidated for use in one or more functional kit(s)60, 64. The kits can take various forms and the arrangement and contentsof the kits can vary. In the illustrated embodiments, each kit 60, 64comprise a sterile, wrapped assembly. Each kit 60, 64 includes aninterior tray 62 made, e.g., from die cut cardboard, plastic sheet, orthermo-formed plastic material, which hold the contents. Kits 60, 64also desirably includes instructions for use 58 for using the contentsof the kit to carry out the procedures described above, including thesystems and methods incorporating the percutaneous system 10 and/or theimplanted system 11.

The instructions 58 can, of course vary. The instructions 58 may bephysically present in the kits, but can also be supplied separately. Theinstructions 58 can be embodied in separate instruction manuals, or invideo or audio tapes, CD's, and DVD's. The instructions 58 for use canalso be available through an internet web page.

V. THE PERIPHERAL NERVOUS SYSTEM

(Anatomic Overview)

As generally shown in FIGS. 14A and 14B, the peripheral nervous systemconsists of nerve fibers and cell bodies outside the central nervoussystem (the brain and the spinal column) that conduct impulses to oraway from the central nervous system. The peripheral nervous system ismade up of nerves (called spinal nerves) that connect the centralnervous system with peripheral structures. The spinal nerves of theperipheral nervous system arise from the spinal column and exit throughintervertebral foramina in the vertebral column (spine). The afferent,or sensory, fibers of the peripheral nervous system convey neuralimpulses to the central nervous system from the sense organs (e.g., theeyes) and from sensory receptors in various parts of the body (e.g., theskin, muscles, etc.). The efferent, or motor, fibers convey neuralimpulses from the central nervous system to the effector organs (musclesand glands).

The somatic nervous system (SNS) is the part of the peripheral nervoussystem associated with the voluntary control of body movements throughthe action of skeletal muscles, and with reception of external stimuli,which helps keep the body in touch with its surroundings (e.g., touch,hearing, and sight). The system includes all the neurons connected withskeletal muscles, skin and sense organs. The somatic nervous systemconsists of efferent nerves responsible for sending central nervoussignals for muscle contraction. A somatic nerve is a nerve of thesomatic nervous system.

A. Spinal Nerves

A typical spinal nerve arises from the spinal cord by rootlets whichconverge to form two nerve roots, the dorsal (sensory) root and theventral (motor) root. The dorsal and ventral roots unite into a mixednerve trunk that divides into a smaller dorsal (posterior) primary ramusand a much larger ventral (anterior) primary ramus. The posteriorprimary rami serve a column of muscles on either side of the vertebralcolumn, and a narrow strip of overlying skin. All of the other muscleand skin is supplied by the anterior primary rami.

The nerve roots that supply or turn into peripheral nerves can begenerally categorized by the location on the spine where the roots exitthe spinal cord, i.e., as generally shown in FIG. 15A, cervical(generally in the head/neck, designated C1 to C8), thoracic (generallyin chest/upper back, designated T1 to T12), lumbar (generally in lowerback, designated L1 to L5); and sacral (generally in the pelvis,designated S1 to S5). All peripheral nerves can be traced back (distallytoward the spinal column) to one or more of the spinal nerve roots ineither the cervical, thoracic, lumbar, or sacral regions of the spine.The neural impulses comprising pain felt in a given muscle or cutaneousregion of the body pass through spinal nerves and (usually) one or morenerve plexuses. For this reason, the spinal nerves will sometimes becalled in shorthand for the purpose of description “nerves of passage.”The spinal nerves begin as roots at the spine, and can form trunks thatdivide by divisions or cords into branches that innervate skin andmuscles.

Spinal nerves have motor fibers and sensory fibers. The motor fibersinnervate certain muscles, while the sensory fibers innervate certainareas of skin. A skin area innervated by the sensory fibers of a singlenerve root is known as a dermatome. A group of muscles primarilyinnervated by the motor fibers of a single nerve root is known as amyotome. Although slight variations do exist, dermatome and myotomepatterns of distribution are relatively consistent from person toperson.

Each muscle in the body is supplied by a particular level or segment ofthe spinal cord and by its corresponding spinal nerve. The muscle, andits nerve make up a myotome. This is approximately the same for everyperson and are as follows:

C3, 4 and 5 supply the diaphragm (the large muscle between the chest andthe belly that we use to breath).

C5 also supplies the shoulder muscles and the muscle that we use to bendour elbow.

C6 is for bending the wrist back.

C7 is for straightening the elbow.

C8 bends the fingers.

T1 spreads the fingers.

T1-T12 supplies the chest wall & abdominal muscles.

L2 bends the hip.

L3 straightens the knee.

L4 pulls the foot up.

L5 wiggles the toes.

S1 pulls the foot down.

S3, 4 and 5 supply the bladder, bowel, and sex organs and the anal andother pelvic muscles.

Dermatome is a Greek word which literally means “skin cutting”. Adermatome is an area of the skin supplied by nerve fibers originatingfrom a single dorsal nerve root. The dermatomes are named according tothe spinal nerve which supplies them. The dermatomes form into bandsaround the trunk (see FIGS. 15B and 15C), but in the limbs theirorganization can be more complex as a result of the dermatomes being“pulled out” as the limb buds form and develop into the limbs duringembryological development.

In the diagrams or maps shown in FIGS. 15B and 15C, the boundaries ofdermatomes are usually sharply defined. However, in life there isconsiderable overlap of innervation between adjacent dermatomes. Thus,if there is a loss of afferent nerve function by one spinal nervesensation from the region of skin which it supplies is not usuallycompletely lost as overlap from adjacent spinal nerves occurs, however,there will be a reduction in sensitivity.

B. Intercostal Nerves

The intercostal nerves (see FIGS. 16A, 16B, and 16C) are the anteriordivisions of the thoracic spinal nerves from the thoracic vertebrae T1to T11. The intercostal nerves are distributed chiefly to the thoracicpleura and abdominal peritoneum and differ from the anterior divisionsof the other spinal nerves in that each pursues an independent coursewithout plexus formation.

The first two nerves supply fibers to the upper limb in addition totheir thoracic branches; the next four are limited in their distributionto the parietes of the thorax; the lower five supply the parietes of thethorax and abdomen. The 7th intercostal nerve terminates at the xyphoidprocess, at the lower end of the sternum. The 10th intercostal nerveterminates at the umbilicus. The twelfth (subcostal) thoracic isdistributed to the abdominal wall and groin.

Branches of a typical intercostal nerve include the ventral primaryramus; lateral cutaneous branches that pass beyond the angles of therubs and innervate the internal and external intercostal musclesapproximately halfway around the thorax; and the anterior cutaneousbranches that supply the skin on the anterior aspect of the thorax andabdomen.

C. Spinal Nerve Plexuses

A nerve plexus is a network of intersecting anterior primary rami. Thesets of anterior primary rami form nerve trunks that ultimately furtherdivide through divisions and then into cords and then into nervebranches serving the same area of the body. The nerve branches aremixed, i.e., they carry both motor and sensory fibers. The branchesinnervate the skin, muscle, or other structures. One example of theentry of a terminal motor nerve branch into muscle is called a motorpoint.

As shown in FIGS. 14A and 14B, there are several nerve plexuses in thebody, including (i) the brachial plexus, which serves the chest,shoulders, arms and hands; (ii) the lumbar plexus, which serves theback, abdomen, groin, thighs, knees, and calves; (iii) the sacralplexus, which serves the buttocks, thighs, calves, and feet; (iv) thecervical plexus, which serves the head, neck and shoulders; and (vi) thesolar plexus, which serves internal organs. The following describes,from an anatomic perspective, the spinal nerves of passage passingthrough the various plexuses, and the muscle and/or skin regions theyinnervate and where pain can be felt.

1. The Brachial Plexus

Most nerves in the upper limb arise from the brachial plexus, as shownin FIGS. 17A and 17B. The brachial plexus begins in the neck (vertebraeC5 through C7), forms trunks, and extends through divisions and cordsinto the axilla (underarm), where nearly all the nerve branches arise.Primary nerve branches of the brachial plexus include themusculocutaneous nerve; the median nerve; the ulnar nerve; the axillarynerve; and the radial nerve.

a. The Musculocutaneous Nerve

The musculocutaneous nerve arises from the lateral cord of the brachialplexus. Its fibers are derived from cervical vertebrae C5, C6. Themusculocutaneous nerve penetrates the coracobrachialis muscle and passesobliquely between the biceps brachii and the brachialis, to the lateralside of the arm. Just above the elbow, the musculocutaneous nervepierces the deep fascia lateral to the tendon of the biceps brachiicontinues into the forearm as the lateral antebrachial cutaneous nerve.In its course through the arm, the musculocutaneous nerve innervates thecoracobrachialis, biceps brachii, and the greater part of thebrachialis.

b. The Median Nerve

The median nerve is formed from parts of the medial and lateral cords ofthe brachial plexus, and continues down the arm to enter the forearmwith the brachial artery. It originates from the brachial plexus withroots from cervical vertebrae C5, C6, C7 and thoracic vertebra T1. Themedian nerve innervates all of the flexors in the forearm, except flexorcarpi ulnaris and that part of flexor digitorum profundus that suppliesthe medial two digits. The latter two muscles are supplied by the ulnarnerve of the brachial plexus. The median nerve is the only nerve thatpasses through the carpal tunnel, where it may be compressed to causecarpal tunnel syndrome.

The main portion of the median nerve supplies the following muscles: (i)the superficial group comprising pronator teres muscle; flexor carpiradialis muscle; palmaris longus muscle; and (ii) the intermediate groupcomprising flexor digitorum superficialis muscle.

The anterior interosseus branch of the median nerve supplies the deepgroup comprising flexor digitorum profundus muscle (lateral half);flexor pollicis longus muscle; and pronator quadratus.

In the hand, the median nerve supplies motor innervation to the 1st and2nd lumbrical muscles. It also supplies the muscles of the thenareminence by a recurrent thenar branch. The rest of the intrinsic musclesof the hand are supplied by the ulnar nerve of the brachial plexus.

The median nerve innervates the skin of the palmar side of the thumb,the index and middle finger, half the ring finger, and the nail bed ofthese fingers. The lateral part of the palm is supplied by the palmarcutaneous branch of the median nerve, which leaves the nerve proximal tothe wrist creases. The palmar cutaneous branch travels in a separatefascial groove adjacent to the flexor carpi radialis and thensuperficial to the flexor retinaculum. It is therefore spared in carpaltunnel syndrome.

c. The Ulnar Nerve

The ulnar nerve comes from the medial cord of the brachial plexus, anddescends on the posteromedial aspect of the humerus. It goes behind themedial epicondyle, through the cubital tunnel at the elbow (where it isvulnerable to injury for a few centimeters, just above the joint). Onemethod of injuring the nerve is to strike the medial epicondyle of thehumerus from posteriorly, or inferiorly with the elbow flexed. The ulnarnerve is trapped between the bone and the overlying skin at this point.This is commonly referred, to as hitting one's “funny bone.”

The ulnar nerve is the largest nerve not protected by muscle or bone inthe human body. The ulnar nerve is the only unprotected nerve that doesnot serve a purely sensory function. The ulnar nerve is directlyconnected to the little finger, and the adjacent half of the ringfinger, supplying the palmar side of these fingers, including both frontand back of the tips, as far back as the fingernail beds.

The ulnar nerve and its branches innervate muscles in the forearm andhand. In the forearm, the muscular branches of ulnar nerve innervatesthe flexor carpi ulnaris and the flexor digitorum profundus (medialhalf). In the hand, the deep branch of ulnar nerve innervates hypothenarmuscles; opponens digiti minimi; abductor digiti minimi; flexor digitiminimi brevis; adductor pollicis; flexor pollicis brevis (deep head);the third and fourth lumbrical muscles; dorsal interossei; palmarinterossei. In the hand, the superficial branch of ulnar nerveinnervates palmaris brevis.

The ulnar nerve also provides sensory innervation to the fifth digit andthe medial half of the fourth digit, and the corresponding part of thepalm. The Palmar branch of ulnar nerve supplies cutaneous innervation tothe anterior skin and nails. The dorsal branch of ulnar nerve suppliescutaneous innervation to the posterior skin (except the nails).

d. The Axillary Nerve

The axillary nerve comes off the posterior cord of the brachial plexusat the level of the axilla (armpit) and carries nerve fibers fromvertebrae C5 and C6. The axillary nerve travels through the quadrangularspace with the posterior circumflex humeral artery and vein. It suppliestwo muscles: the deltoid (a muscle of the shoulder), and the teres minor(one of the rotator cuff muscles). The axillary nerve also carriessensory information from the shoulder joint, as well as from the skincovering the inferior region of the deltoid muscle, i.e., the“regimental badge” area (which is innervated by the superior lateralcutaneous nerve branch of the axillary nerve). When the axillary nervesplits off from the posterior cord, the continuation of the cord is theradial nerve.

e. The Radial Nerve

The radial nerve supplies the upper limb, supplying the triceps brachiimuscle of the arm, as well as all twelve muscles in the posteriorosteofascial compartment of the forearm, as well as the associatedjoints and overlying skin. The radial nerve originates from theposterior cord of the brachial plexus with roots from cervical vertebraeC5, C6, C7, C8 and thoracic vertebra T1.

Cutaneous innervation is provided by the following nerves: (i) posteriorcutaneous nerve of arm (originates in axilla); (ii) inferior lateralcutaneous nerve of arm (originates in arm); and (iii) posteriorcutaneous nerve of forearm (originates in arm). The superficial branchof the radial nerve provides sensory innervation to much of the back ofthe hand, including the web of skin between the thumb and index finger.

Muscular branches of the radial nerve innervate the triceps brachii;anconeus brachioradialis; and the extensor carpi radialis longus.

The deep branch of the radial nerve innervates the extensor carpiradialis brevis; supinator; posterior interosseous nerve (a continuationof the deep branch after the supinator): extensor digitorum; extensordigiti minimi; extensor carpi ulnaris; abductor pollicis longus;extensor pollicis brevis; extensor pollicis longus; and extensorindicis.

The radial nerve (and its deep branch) provides motor innervation to themuscles in the posterior compartment of the arm and forearm, which aremostly extensors.

2. Sacral and Lumbar Plexuses

The lumbar plexus (see FIG. 18) is a nervous plexus in the lumbar regionof the body and forms part of the lumbosacral plexus. It is formed bythe ventral divisions of the first four lumbar nerves (L1-L4) and fromcontributions of the subcostal thoracic nerve (T12), which is the last(most inferior) thoracic nerve.

Additionally, the ventral rami of sacral vertebrae S2 and S3 nervesemerge between digitations of the piriformis and coccygeus nuscles. Thedescending part of the lumbar vertebrae L4 nerve unites with the ventralramus of the lumbar vertebrae L5 nerve to form a thick, cordlikelumbosacral trunk. The lumbosacral trunk joins the sacral plexus (seeFIG. 19).

The main nerves of the lower limbs arise from the lumbar and sacralplexuses.

a. Nerves of the Sacral Plexus the Sacral Plexus Provides Motor andSensory Nerves for the Posterior Thigh, Most of the Lower Leg, and theEntire Foot. (1) the Sciatic Nerve

As shown in FIGS. 14A and 19, the sciatic nerve (also known as theischiatic nerve) arises from the sacral plexus. It is the longest andwidest single nerve in the human body. It begins in the lower back andruns through the buttock and down the lower limb. The sciatic nervesupplies nearly the whole of the skin of the leg, the muscles of theback of the thigh, and those of the leg and foot. It is derived fromspinal nerves L4 through S3. It contains fibers from both the anteriorand posterior divisions of the lumbosacral plexus.

The nerve gives off articular and muscular branches. The articularbranches (rami articulares) arise from the upper part of the nerve andsupply the hip-joint, perforating the posterior part of its capsule;they are sometimes derived from the sacral plexus. The muscular branches(rami musculares) innervate the following muscles of the lower limb:biceps femoris, semitendinosus, semimembranosus, and adductor magnus.The nerve to the short head of the biceps femoris comes from the commonperoneal part of the sciatic, while the other muscular branches arisefrom the tibial portion, as may be seen in those cases where there is ahigh division of the sciatic nerve.

The muscular branch of the sciatic nerve eventually gives off the tibialnerve (shown in FIG. 1A) and common peroneal nerve (also shown in FIG.14A), which innervates the muscles of the (lower) leg. The tibial nervegoes on to innervate all muscles of the foot except the extensordigitorum brevis (which is innervated by the peroneal nerve).

b. Nerves of the Lumbar Plexus

The lumbar plexus (see FIG. 18) provides motor, sensory, and autonomicfibres to gluteal and inguinal regions and to the lower extremities. Thegluteal muscles are the three muscles that make up the buttocks: thegluteus maximus muscle, gluteus medius muscle and gluteus minimusmuscle. The inguinal region is situated in the groin or in either of thelowest lateral regions of the abdomen.

(1) The Iliohypogastric Nerve

The iliohypogastric nerve (see FIG. 18) runs anterior to the psoas majoron its proximal lateral border to run laterally and obliquely on theanterior side of quadratus lumborum. Lateral to this muscle, it piercesthe transversus abdominis to run above the iliac crest between thatmuscle and abdominal internal oblique. It gives off several motorbranches to these muscles and a sensory branch to the skin of thelateral hip. Its terminal branch then runs parallel to the inguinalligament to exit the aponeurosis of the abdominal external oblique abovethe external inguinal ring where it supplies the skin above the inguinalligament (i.e. the hypogastric region) with the anterior cutaneousbranch.

(2) The Ilioinguinal Nerve

The ilioinguinal nerve (see FIG. 18) closely follows the iliohypogastricnerve on the quadratus lumborum, but then, passes below it to run at thelevel of the iliac crest. It pierces the lateral abdominal wall and runsmedially at the level of the inguinal ligament where it supplies motorbranches to both transversus abdominis and sensory branches through theexternal inguinal ring to the skin over the pubic symphysis and thelateral aspect of the labia majora or scrotum.

(3) The Genitofemoral Nerve

The genitofemoral nerve (see FIG. 18) pierces psoas major anteriorlybelow the former two nerves to immediately split into two branches thatrun downward on the anterior side of the muscle. The lateral femoralbranch is purely sensory. It pierces the vascular lacuna near thesaphenous hiatus and supplies the skin below the inguinal ligament (i.e.proximal, lateral aspect of femoral triangle). The genital branchdiffers in males and females. In males it runs in the spermatic cord andin females in the inguinal canal together with the teres uteri ligament.It then sends sensory branches to the scrotal skin in males and thelabia majora in females. In males it supplies motor innervation to thecremaster.

(4) The Lateral Cutaneous Femoral Nerve

The lateral cutaneous femoral nerve (see FIG. 18) pierces psoas major onits lateral side and runs obliquely downward below the iliac fascia.Medial to the anterior superior iliac spine it leaves the pelvic areathrough the lateral muscular lacuna. In the thigh it briefly passesunder the fascia lata before it breaches the fascia and supplies theskin of the anterior thigh.

(5) The Obturator Nerve

The obturator nerve (see FIG. 18) leaves the lumbar plexus and descendsbehind psoas major on it medial side, then follows the linea terminalisand exits through the obturator canal. In the thigh, it sends motorbranches to obturator externus before dividing into an anterior and aposterior branch, both of which continues distally. These branches areseparated by adductor brevis and supply all thigh adductors with motorinnervation: pectineus, adductor longus, adductor brevis, adductormagnus, adductor minimus, and gracilis. The anterior branch contributesa terminal, sensory branch which passes along the anterior border ofgracilis and supplies the skin on the medial, distal part of the thigh.

(6) The Femoral Nerve

The femoral nerve (see FIG. 18 and also FIG. 19A) is the largest andlongest nerve of the lumbar plexus. It gives motor innervation toiliopsoas, pectineus, sartorius, and quadriceps femoris, and sensoryinnervation to the anterior thigh, posterior lower leg, and hindfoot. Itruns in a groove between psoas major and iliacus giving off branches toboth muscles. In the thigh it divides into numerous sensory and muscularbranches and the saphenous nerve, its long sensory terminal branch whichcontinues down to the foot.

3. The Cervical Plexus

The cervical plexus (see FIG. 20) is a plexus of the ventral rami of thefirst four cervical spinal nerves which are located from C1 to C4cervical segment in the neck. They are located laterally to thetransverse processes between prevertebral muscles from the medial sideand vertebral (m. scalenus, m. levator scapulae, m. splenius cervicis)from lateral side. Here there is anastomosis with accessory nerve,hypoglossal nerve and sympathetic trunk.

The cervical plexus is located in the neck, deep to sternocleidomastoid.Nerves formed from the cervical plexus innervate the back of the head,as well as some neck muscles. The branches of the cervical plexus emergefrom the posterior triangle at the nerve point, a point which liesmidway on the posterior border of the Sternocleidomastoid.

The nerves formed by the cervical plexus supply the back of the head,the neck and the shoulders. The face is supplied by a cranial nerve, thetrigeminal nerve. The upper four posterior primary rami are larger thanthe anterior primary rami. The C1 posterior primary ramus does notusually supply the skin. The C2 posterior primary ramus forms thegreater occipital nerve which supplies the posterior scalp. The upperfour anterior primary rami form the cervical plexus. The cervical plexussupplies the skin over the anterior and lateral neck to just below theclavicle. The plexus also supplies the muscles of the neck including thescalenes, the strap muscles, and the diaphragm.

The cervical plexus has two types of branches: cutaneous and muscular.

The cutaneous branches include the lesser occipital nerve, whichinnervates lateral part of occipital region (C2 nerve only); the greatauricular nerve, which innervates skin near concha auricle and externalacoustic meatus (C2 and C3 nerves); the transverse cervical nerve, whichinnervates anterior region of neck (C2 and C3 nerves); and thesupraclavicular nerves, which innervate region of suprascapularis,shoulder, and upper thoracic region (C3,C4 Nerves)

The muscular branches include the ansa cervicalis (loop formed fromC1-C3), etc. (geniohyoid (C1 only), thyrohyoid (C1 only), sternothyroid,sternohyoid, omohyoid); phrenic (C3-C5 (primarily C4)), which innervatesthe diaphragm; the segmental branches (C1-C4), which innervate theanterior and middle scalenes.

4. The Solar Plexus

The solar plexus (see FIG. 21) is a dense cluster of nerve cells andsupporting tissue, located behind the stomach in the region of theceliac artery just below the diaphragm. It is also known as the celiacplexus. Rich in ganglia and interconnected neurons, the solar plexus isthe largest autonomic nerve center in the abdominal cavity. Throughbranches it controls many vital functions such as adrenal secretion andintestinal contraction.

Derived from the solar plexus are the phrenic plexus (producingcontractions of the diaphragm, and providing sensory innervation formany components of the mediastinum and pleura); the renal plexuses(affecting renal function); the spermatic plexus (affecting function ofthe testis); as well as the gastric plexus; the hepatic plexus; thesplenic plexus; the superior mesenteric plexus; and the aortic plexus.

VI. THE SYSTEM

The various aspects of the invention will be described in connectionwith the placement of one or more leads 12 having one or more electrodes14, in muscle, and in electrical proximity but away from nerves, forimproved recruitment of targeted nerves for therapeutic purposes, suchas for the treatment of pain. That is because the features andadvantages that arise due to the invention are well suited to thispurpose. It is to be appreciated that regions of pain can include any orall portions of the body, including arms and legs in both humans andanimals.

A. Stimulation of Nerves of Passage

FIG. 22 shows a typical “motor point” system and method for stimulatinga nerve or muscle A by placing a lead 12(A) with its electrode 14(A)close to motor point A. As previously described, a motor point A is thelocation where the innervating spinal nerve enters the muscle. At thatlocation, the electrical stimulation intensity required to elicit a fullcontraction is at the minimum. Any other location in the muscle wouldrequire more stimulation intensity to elicit the same musclecontraction.

FIG. 23 shows a “nerves of passage” system and method, that is unlikethe “motor point” system and method shown in FIG. 22, and whichincorporates the features of the invention. As shown in FIG. 23, thesystem and method identifies a region where there is a localmanifestation of pain. The region of pain can comprise, e.g., skin,bone, a joint, or muscle. The system and method identify one or morespinal nerves that are located anatomically upstream or cranial to theregion where pain is manifested, through which neural impulsescomprising the pain pass. A given spinal nerve that is identified cancomprise a nerve trunk located in a nerve plexus, or a divisions and/ora cord of a nerve trunk, or a nerve branch, provided that it is upstreamor cranial of where the nerve innervates the region affected by thepain. The given spinal nerve can be identified by medical professionalsusing textbooks of human anatomy along with their knowledge of the siteand the nature of the pain or injury, as well as by physical manipulatedand/or imaging, e.g., by ultrasound, fluoroscopy, or X-ray examination,of the region where pain is manifested. A desired criteria of theselection includes identifying the location of muscle in electricalproximity to but spaced away from the nerve or passage, which muscle canbe accessed by placement of one or more stimulation electrodes, aided ifnecessary by ultrasonic or electro-location techniques. The nerveidentified comprises a targeted “nerve of passage.” The muscleidentified comprises the “targeted muscle.” In a preferred embodiment,the electrodes are percutaneously inserted using percutaneous leads.

The system and method place the one or more leads 12(B) with itselectrode 14(B) in the targeted muscle in electrical proximity to butspaced away from the targeted nerve of passage. The system and methodapply electrical stimulation through the one or more stimulationelectrodes to electrically activate or recruit the targeted nerve ofpassage that conveys the neural impulses comprising the pain to thespinal column.

The system and method can apply electrical stimulation to nerves ofpassage throughout the body. For example, the nerves of passage cancomprise one or more spinal nerves in the brachial plexus, to treat painin the chest, shoulders, arms and hands; and/or one or more spinalnerves in the lumbar plexus, to treat pain in the back, abdomen, groin,thighs, knees, and calves; and/or one or more spinal nerves in thesacral plexus, to treat pain in the buttocks, thighs, calves, and feet;and/or one or more spinal nerves in the cervical plexus, to treat painin the head, neck and shoulders; and/or one or more spinal nerves in thesolar plexus, to treat pain or dysfunction in internal organs.

For example, if the pinky finger hurts, the system and method canidentify and stimulate the ulnar nerve at a location that it is upstreamor cranial of where the nerve innervates the muscle or skin of the pinkyfinger, e.g., in the palm of the hand, forearm, and/or upper arm. Ifelectrical stimulation activates the target nerve of passagesufficiently at the correct intensity, then the patient will feel acomfortable tingling sensation called a paresthesia in the same regionas their pain, which overlap with the region of pain and/or otherwisereduce pain.

It is to be appreciated that the sensation could be described with otherwords such as buzzing, thumping, etc. Evoking paresthesias in the regionof pain confirms correct lead placement and indicates stimulus intensityis sufficient to reduce pain. Inserting a lead 12 percutaneously allowsthe lead 12 to be placed quickly and easily, and placing the lead 12 ina peripheral location, i.e., muscle, where it is less likely to bedislodged, addresses the lead migration problems of spinal cordstimulation that result in decreased paresthesia coverage, decreasedpain relief, and the need for frequent patient visits for reprogramming.

Placing the lead 12 percutaneously in muscle in electrical proximity tobut spaced away from the targeted nerve of passage minimizecomplications related to lead placement and movement. In a percutaneoussystem, an electrode lead 12, such as a coiled fine wire electrode leadmay be used because it is minimally-invasive and well suited forplacement in proximity to a nerve of passage. The lead can be sized andconfigured to withstand mechanical forces and resist migration duringlong-term use, particularly in flexible regions of the body, such as theshoulder, elbow, and knee.

B. The Lead

As FIG. 24A shows, the electrode lead can comprise, e.g., a fine wireelectrode 14, paddle electrode, intramuscular electrode, orgeneral-purpose electrode, inserted via a needle introducer 30 orsurgically implanted in proximity of a targeted nerve of passage. Onceproper placement is confirmed, the needle introducer 30 may be withdrawn(as FIGS. 24B and 24C show), leaving the electrode in place. Stimulationmay also be applied through a penetrating electrode, such as anelectrode array comprised of any number (i.e., one or more) ofneedle-like electrodes that are inserted into the target site. In bothcases, the lead may placed using a needle-like introducer 30, allowingthe lead/electrode placement to be minimally invasive.

In a representative embodiment, the lead 12 comprises a thin, flexiblecomponent made of a metal and/or polymer material. By “thin,” it iscontemplated that the lead should not be greater than about 0.75 mm(0.030 inch) in diameter.

The lead 12 can comprise, e.g., one or more coiled metal wires with inan open or flexible elastomer core. The wire can be insulated, e.g.,with a biocompatible polymer film, such as polyfluorocarbon, polyimide,or parylene. The lead is desirably coated with a textured,bacteriostatic material, which helps to stabilize the lead in a way thatstill permits easy removal at a later date and increases tolerance.

The lead 12 may be electrically insulated everywhere except at one(monopolar), or two (bipolar), or three (tripolar), for example,conduction locations near its distal tip. Each of the conductionlocations may be connected to one or more conductors that run the lengthof the lead and lead extension 16 (see FIG. 24C), proving electricalcontinuity from the conduction location through the lead 12 to anexternal pulse generator or stimulator 28 (see FIG. 24C) or an implantedpulse generator or stimulator 28 (see FIG. 24D).

The conduction location or electrode 14 may comprise a de-insulated areaof an otherwise insulated conductor that runs the length of an entirelyinsulated electrode. The de-insulated conduction region of the conductorcan be formed differently, e.g., it can be wound with a different pitch,or wound with a larger or smaller diameter, or molded to a differentdimension. The conduction location or the electrode 14 may comprise aseparate material (e.g., metal or a conductive polymer) exposed to thebody tissue to which the conductor of the wire is bonded.

The lead 12 is desirably provided in a sterile package 62 (see FIG. 25),and may be pre-loaded in the introducer needle 30. The package 62 cantake various forms and the arrangement and contents of the package 62.As shown in FIG. 12, the package 62 comprises a sterile, wrappedassembly. The package 62 includes an interior tray made, e.g., from diecut cardboard, plastic sheet, or thermo-formed plastic material, whichhold the contents. The package 62 also desirably includes instructionsfor use 58 for using the contents of the package to carry out the leadlocation and placement procedures, as will be described in greaterdetail below.

The lead 12 desirably possess mechanical properties in terms offlexibility and fatigue life that provide an operating life free ofmechanical and/or electrical failure, taking into account the dynamicsof the surrounding tissue (i.e., stretching, bending, pushing, pulling,crushing, etc.). The material of the electrode 14 desirably discouragesthe in-growth of connective tissue along its length, so as not toinhibit its withdrawal at the end of its use. However, it may bedesirable to encourage the in-growth of connective tissue at the distaltip of the electrode, to enhance its anchoring in tissue.

One embodiment of the lead 12 shown in FIG. 26A may comprise a minimallyinvasive coiled fine wire lead 12 and electrode 14. The electrode 14 mayalso include, at its distal tip, an anchoring element 48. In theillustrated embodiment, the anchoring element 48 takes the form of asimple barb or bend (see also FIG. 24C). The anchoring element 48 issized and configured so that, when in contact with tissue, it takespurchase in tissue, to resist dislodgement or migration of the electrodeout of the correct location in the surrounding tissue. Desirably, theanchoring element 48 is prevented from fully engaging body tissue untilafter the electrode 14 has been correctly located and deployed.

An alternative embodiment of an electrode lead 12 shown in FIGS. 27A and27B, may also include, at or near its distal tip or region, one or moreanchoring element(s) 70. In the illustrated embodiment, the anchoringelement 70 takes the form of an array of shovel-like paddles or scallops76 proximal to the proximal-most electrode 14 (although a paddle 76 orpaddles could also be proximal to the distal most electrode 14, or couldalso be distal to the distal most electrode 14). The paddles 76 as shownare sized and configured so they will not cut or score the surroundingtissue. The anchoring element 70 is sized and configured so that, whenin contact with tissue, it takes purchase in tissue, to resistdislodgement or migration of the electrode out of the correct locationin the surrounding tissue (e.g., muscle 54). Desirably, the anchoringelement 70 is prevented from fully engaging body tissue until after theelectrode 14 has been deployed. The electrode is not deployed untilafter it has been correctly located during the implantation (leadplacement) process, as previously described. In addition, the lead 12may include one or more ink markings 74, 75 (shown in FIG. 27A) to aidthe physician in its proper placement.

Alternatively, or in combination, stimulation may be applied through anytype of nerve cuff (spiral, helical, cylindrical, book, flat interfacenerve electrode (FINE), slowly closing FINE, etc.), paddle (orpaddle-style) electrode lead, cylindrical electrode lead, and/or otherlead that is surgically or percutaneously placed within muscle at thetarget site.

In all cases, the lead may exit through the skin and connect with one ormore external stimulators 28 (shown in FIG. 24C), or the lead(s) may berouted subcutaneously to one or more implanted pulse generators 28(shown in FIG. 24D), or they may be connected as needed to internal andexternal coils for RF (Radio Frequency) wireless telemetrycommunications or an inductively coupled telemetry to control theimplanted pulse generator. As shown in FIG. 24D, the implanted pulsegenerator 28 may be located some distance (remote) from the electrode14, or an implanted pulse generator may be integrated with anelectrode(s) (not shown), eliminating the need to route the leadsubcutaneously to the implanted pulse generator.

The introducer 30 (see FIG. 24A) may be insulated along the length ofthe shaft, except for those areas that correspond with the exposedconduction surfaces of the electrode 14 housed inside the introducer 30.These surfaces on the outside of the introducer 30 are electricallyisolated from each other and from the shaft of the introducer 30. Thesesurfaces may be electrically connected to a connector 64 at the end ofthe introducer body (see FIG. 24A). This allows connection to anexternal stimulator 28 (shown in FIG. 24A) during the implantationprocess. Applying stimulating current through the outside surfaces ofthe introducer 30 provides a close approximation to the response thatthe electrode 14 will provide when it is deployed at the currentlocation of the introducer 30.

The introducer 30 may be sized and configured to be bent by hand priorto its insertion through the skin. This will allow the physician toplace lead 12 in a location that is not in an unobstructed straight linewith the insertion site. The construction and materials of theintroducer 30 allow bending without interfering with the deployment ofthe lead 12 and withdrawal of the introducer 30, leaving the lead 12 inthe tissue.

C. Insertion of the Lead

Representative lead insertion techniques will now be described to placean electrode lead 12 in a desired location in muscle in electricalproximity to but spaced away from a nerve of passage. It is this leadplacement that makes possible the stimulation of the targeted nerve ornerves of passage with a single lead 12 to provide pain relief.

Instructions for use 58 (see FIG. 25) can direct use of system andmethod for the placement of a lead 12 in muscle in electrical proximityto but spaced away from the nerve or nerves of passage for improvedrecruitment of target nerves, e.g., with the placement of one or moreleads 12. The instructions for use may include instructions for placinga lead 12 for the activation of the targeted nerve of passage in asystem for the relief of pain, for example. The instructions for use mayalso include instructions for recording stimulus parameters, includingintensity associated with a first sensation of stimulation, a firstnoticeable muscle contraction, and a maximum tolerable contraction atmultiple locations, which can be used to aid in determining desiredstimulation parameters for optimal stimulation.

The instructions 58 can, of course vary. The instructions 58 may bephysically present in a kits holding the lead 12 (as FIG. 25 shows), butcan also be supplied separately. The instructions 58 can be embodied inseparate instruction manuals, or in video or audio tapes, CD's, andDVD's. The instructions 58 for use can also be available through aninternet web page.

To determine the optimal placement for the lead 12, test stimulation maybe delivered through needle electrodes, and muscle responses may beobserved. The motor point(s) of the target muscle(s) may be locatedfirst in order to confirm that the muscles are innervated. Needleelectrodes may be used because they can be easily repositioned until theoptimal location to deliver stimulation is determined.

At least one lead(s) may be placed in muscle tissue near a targetednerve of passage. The lead may be inserted via the introducer 30 inconventional fashion, which may be similar in size and shape to ahypodermic needle. The introducer 30 may be any size. In a preferredembodiment, the introducer 30 may range in size from 17 gauge to 26gauge. Prior to inserting the introducer 30, the insertion site may becleaned with a disinfectant (e.g. Betadine, 2% Chlorhexidine/80%alcohol, 10% povidone-iodine, or similar agent). A local anesthetic(s)may be administered topically and/or subcutaneously to the area in whichthe electrode and/or introducer will be inserted.

The position of the electrodes may be checked by imaging techniques,such as ultrasound, fluoroscopy, or X-rays. Following placement of thelead(s), the portion of the leads which exit the skin may be secured tothe skin using covering bandages and/or adhesives.

Electrical stimulation may be applied to the targeted nerve of passageduring and after placement of the electrode to determine whetherstimulation of the targeted nerve of passage can generate comfortablesensations or paresthesias that overlap with the region of pain and/orreduce pain. The pain may be perceived to be contained within a specificpart(s) of the body and/or it may be perceived to be located outside ofthe body, as may be the case in persons with amputations who havephantom pain or pain in the amputated (or phantom) limb(s).

In a percutaneous system 10 (as FIGS. 24A to 24D show, the lead 12 maybe percutaneously placed near the targeted nerve of passage and exit ata skin puncture site 16. A trial or screening test may be conducted in aclinical setting (e.g. an office of a clinician, a laboratory, aprocedure room, an operating room, etc.). During the trial, the lead iscoupled to an external pulse generator 28 and temporary percutaneousand/or surface return electrodes, to confirm paresthesia coverage and/orpain relief of the painful areas.

If the clinical screening test is successful, the patient may proceed toa home-trial coupled to an external pulse generator 28 (as shown in FIG.24C) and temporary percutaneous and/or surface return electrodes, todetermine if pain relief can be sustained in the home environment. Thetrial period may range from minutes to hours to days to weeks to months.The preferred trial period may be between 3 and 21 days.

If either the screening test or home trial is unsuccessful, the lead 12may be quickly and easily removed.

However, if the screening test and/or home-trial are successful, thepatient's percutaneous system may be converted into a fully implantedsystem (as shown in FIG. 24D) by replacing the external pulse generatorwith an implantable pulse generator 28 (the housing of which serves as areturn electrode).

Alternatively, it may be preferred to use a percutaneous system(s) as atherapy without proceeding to a fully implantable system. It is also tobe appreciated that a home-trial is not a requirement for either thepercutaneous system or a fully implanted system.

The duration of therapy for a percutaneous system may range from minutesto days to weeks to months to multiple years, but a preferred embodimentincludes a duration ranging from 1 to 12 weeks.

Electrical stimulation is applied between the lead and return electrodes(uni-polar mode). Regulated current is the preferred type ofstimulation, but other type(s) of stimulation (e.g. non-regulatedcurrent such as voltage-regulated) may also be used. Multiple types ofelectrodes may be used, such as surface, percutaneous, and/orimplantable electrodes. The surface electrodes may be a standard shapeor they may be tailored if needed to fit the contour of the skin.

In a preferred embodiment of a percutaneous system, the surfaceelectrode(s) may serve as the anode(s) (or return electrode(s)), but thesurface electrode(s) may be used as the cathode(s) (active electrode(s))if necessary. When serving as a return electrode(s), the location of theelectrode(s) is not critical and may be positioned anywhere in thegeneral vicinity, provided that the current path does not cross theheart. If a surface electrode(s) serves as an active electrode(s), it(they) may be positioned near the target stimulation area(s) (e.g. onthe skin surface over the target nerve or passage).

The electrode lead may be placed via multiple types of approaches. Inone embodiment, the approach may be similar needle placement forelectromyography (EMG).

For example (as shown in FIG. 28A), if the targeted nerve of passageincludes nerves of the brachial plexus, the approach can include:

Place the patient in a comfortable and/or appropriate position with headturned away from the lead insertion site.

Prepare the lead insertion site with antiseptic and local subcutaneousanesthetic (e.g., 2% lidocaine).

Locate the site of skin puncture with appropriate landmarks, such as theclavical, coracoid process, and axilla, as necessary.

Insert a sterile percutaneous electrode lead 12 preloaded in theintroducer needle 30 at a predetermined angle based on landmarks used.

Place a surface stimulation return electrode in proximity of the area inwhich the percutaneous lead 12 has been placed. Test stimulation will beapplied to the lead 12, with the surface electrode providing a returnpath. The surface electrode may be placed adjacent to the lead. Itsposition is not critical to the therapy and it can be moved throughoutthe therapy to reduce the risk of skin irritation.

Couple the lead 12 to the external pulse generator 28 and to the returnelectrode. Set the desired stimulation parameters. Test stimulation maybe delivered using a current-regulated pulse generator, for example. Theexternal pulse generator 28 may be programmed to 4 mA, 100 μs, 100 Hz,and an on-off duty cycle of 0.25 sec., as a non-limiting example.

Advance the introducer slowly until the subject reports the first evokedsensation in the region experiencing pain. Progressively reduce thestimulus amplitude and advance the introducer more slowly until thesensation can be evoked in the painful region at a predeterminedstimulus amplitude (e.g., 1 mA). Stop the advancement of the introducer,and increase the stimulus amplitude in small increments (e.g., 0.1 mA)until the stimulation-evoked tingling sensation (paresthesia) expands tooverlay the entire region of pain.

Withdraw the introducer 30, leaving the percutaneous lead 12 inproximity but away from the target nerve (see FIG. 28B).

Cover the percutaneous exit site and lead 12 with a bandage. A bandagemay also be used to secure the external portion of the lead 12 (or anextension cable used to couple the lead 12 to the external pulsegenerator) to the skin. It is expected the length of time to place thelead 12 to be less than 10 minutes, although the process may be shorteror longer.

Vary the stimulus amplitude in small steps (e.g., 0.1-0.5 mA) todetermine the thresholds at which stimulation evokes first sensation(TSEN), sensation (paresthesia) superimposed on the region of pain(TSUP), muscle twitch (TMUS) of the target muscle (innervated or notinnervated by the target nerve), and maximum comfortable sensation(TMAX). Query the subject at each stimulus amplitude to determinesensation level, and visually monitor muscle response. Record theresults.

It is possible that stimulation intensity may need to be increasedslightly during the process due to causes such as habituation or thesubject becoming accustomed to sensation, but the need for increasedintensity is unlikely and usually only occurs after several days toweeks to months as the tissue encapsulates and the subject accommodatesto stimulation. It is to be appreciated that the need for increasedintensity could happen at any time, even years out, which would likelybe due to either lead migration or habituation, but may also be duereasons ranging from nerve damage to plasticity/reorganization in thecentral nervous system.

If paresthesias cannot be evoked with the initial lead placement,redirect the introducer 30.

If sensations still cannot be evoked in a given subject, then the muscletwitch response of the muscle innervated or not innervated by the targetnerve may be used to guide lead placement and then increase stimulusintensity until sufficient paresthesias are elicited in the painfulregion. Minimal muscle contraction may be acceptable if it is welltolerated by the patient in exchange for significant pain relief and ifit does not lead to additional discomfort or fatigue.

If stimulation evokes muscle contraction at a lower stimulus thresholdthan paresthesia (e.g. if TMUS≦TSUP) and contraction leads todiscomfort, then a lower stimulus frequency (e.g., 12 Hz) may be usedbecause low frequencies (e.g., 4-20 Hz) have been shown to minimizediscomfort due to muscle contraction and provide >50% relief of shoulderpain in stroke patients while still inhibiting transmission of painsignals in the central nervous system in animals. If continued musclecontraction leads to pain due to fatigue, change the duty cycle, usingparameters shown to reduce muscle fatigue and related discomfort in theupper extremity (e.g. 5 s ramp up, 10 s on, 5 s ramp down, 10 s off).

If stimulation fails to elicit paresthesia in all areas of pain, then asecond percutaneous lead (not shown) may need to be placed to stimulatethe nerves that are not activated by the first lead 12.

If stimulation is successful, i.e., if the screening test and/orhome-trial are successful, the patient's percutaneous system (see FIG.14) may be converted into a fully implanted system by replacing theexternal pulse generator 28 with an implantable pulse generator that isimplanted in a convenient area (see FIG. 24D) (e.g., in a subcutaneouspocket over the hip or in the subclavicular area). In one embodiment,the electrode lead 12 used in the screening test and/or home-trial maybe totally removed and discarded, and a new completely implantable leadmay be tunneled subcutaneously and coupled to the implantable pulsegenerator. In an alternative embodiment, a two part lead may beincorporated in the screening test and/or home-trial where theimplantable part is completely under the skin and connected to apercutaneous connector (i.e., extension) that can be discarded afterremoval. The implantable part may then be tunneled and coupled to theimplantable pulse generator, or a new sterile extension may be used tocouple the lead to the implantable pulse generator.

Alternatively, when the targeted nerve of passage includes one or morenerves of the lumbar plexus or sacral plexus, the approach may be eithera posterior (shown in FIG. 29A) or an anterior approach (shown in FIG.30A), similar to those used for regional anesthesia of the same targetednerve of passage, except that the approach is used for placement throughan introducer of stimulation lead(s) in electrical proximity to butspaced away from a nerve of passage, and not for regional anesthesia.Unlike regional anesthesia, the approach to nerves of the lumbar plexusor sacral plexus do not involve the application of anesthesia to thenerve, and, when the introducer is withdrawn, the lead(s) may be leftbehind to desired stimulation of the target nerve of passage.

For example, when the targeted nerve of passage includes the sciaticnerve (see FIG. 31A), the introducer(s) 30 and/or lead(s) 12 may bedirected towards the sciatic nerve using a posterior approach, such asthe transgluteal approach or subgluteal approach, which are both welldescribed and commonly used in regional anesthesiology (Dalens et al.1990; Bruelle et al. 1994; di Benedetto et al. 2001; Gaertner et al.2007).

This approach allows lead placement near a targeted nerve of passagewith a simple, quick (e.g. less than 10 minutes) outpatient procedurethat may be performed in a standard community-based clinic. This makespossible widespread use and provides a minimally-invasive screening testto determine if patients will benefit from the device before receiving afully implanted system.

The landmarks for the transgluteal approach may include the greatertrochanter and the posterior superior iliac spine. The introducer 30 maybe inserted distal (e.g. approximately 2 cm to 6 cm, preferably 4 cm, ina preferred embodiment) to the midpoint between the greater trochanterand the posterior iliac spine. As a non-limiting example of patientpositioning, the patient may be in a lateral decubitus position andtilted slightly forward in a preferred embodiment. The landmarks for thesubgluteal approach may include the greater trochanter and the ischialtuberosity. The introducer may be inserted distal (e.g. approximately 2cm to 6 cm, preferably 4 cm, in the preferred embodiment) to themidpoint between the greater trochanter and the ischial tuberosity.

For example, when the targeted nerve of passage includes the femoralnerve (see FIG. 31A), percutaneous leads 12 may be directed towards thefemoral nerve using an anterior approach. The landmarks may include theinguinal ligament, inguinal crease, and femoral artery. The subject maybe in the supine position with ipsilateral extremity slightly(approximately 10 to 20 degrees) abducted. The introducer may beinserted near the femoral crease but below the inguinal crease andapproximately 1 cm lateral to the pulse of the femoral artery.

The size and shape of tissues, such as the buttocks, surrounding thetarget nerves may vary across subjects, and the approach may be modifiedas needed to accommodate various body sizes and shapes to access thetarget nerve.

In non-amputee patients, introducer placement can be often guided bymuscle response to electrical stimulation, but the muscle response maynot be available in amputees, or may not be available and/or beunreliable in other situations (e.g., a degenerative diseases orcondition such as diabetes of impaired vascular function in which thenerves are slowly degenerating, progressing from the periphery, or dueto trauma).

In these situations, placement may be guided by the individual's reportof stimulus-evoked sensations (paresthesias) as the introducer is placedduring test stimulation. Additionally, the response of remaining musclesto stimulation may also be used to guide placement of the introducer andelectrode.

As shown in FIG. 31B, more than a single lead 12 may be placed around agiven nerve of passage, using either an anterior approach (e.g., femoralnerve) or a posterior approach (e.g., sciatic nerve). As FIGS. 32A, B,and C show, one or more leads 12 can be placed at differentsuperior-inferior positions along a nerve of passage and/or alongdifferent nerves of passage.

As FIG. 29B (anterior approach, e.g., femoral nerve) and 17B (posteriorapproach, e.g., sciatic nerve) show, the lead 12 can be coupled to anexternal pulse generator 28 worn, e.g., on a belt 52, for a trial ortemporary stimulation regime. In this arrangement, the lead 12 iscovered with a bandage 50, and a surface electrode 54 serves as a returnelectrode. The external/percutaneous system shown in FIGS. 29B and 30Bmay be replaced by an implanted system using an implanted pulsegenerator 60 and intramuscular and tunneled leads 62, as shown in FIGS.29C and 30C, respectively. In this arrangement, the case of theimplanted pulse generator 60A comprises the return electrode.

D. Stimulation Parameters

Control of the stimulator and stimulation parameters may be provided byone or more external controllers. In the case of an external stimulator,the controller may be integrated with the external stimulator. Theimplanted pulse generator external controller (i.e., clinicalprogrammer) may be a remote unit that uses RF (Radio Frequency) wirelesstelemetry communications (rather than an inductively coupled telemetry)to control the implanted pulse generator. The external or implantablepulse generator may use passive charge recovery to generate thestimulation waveform, regulated voltage (e.g., 10 mV to 20 V), and/orregulated current (e.g., about 10 pA to about 50 mA). Passive chargerecovery is one method of generating a biphasic, charge-balanced pulseas desired for tissue stimulation without severe side effects due to aDC component of the current.

The neurostimulation pulse may by monophasic, biphasic, and/ormulti-phasic. In the case of the biphasic or multi-phasic pulse, thepulse may be symmetrical or asymmetrical. Its shape may be rectangularor exponential or a combination of rectangular and exponentialwaveforms. The pulse width of each phase may range between e.g., about0.1 μsec. to about 1.0 sec., as non-limiting examples. The preferredneurostimulation waveform is cathodic stimulation (though anodic willwork), biphasic, and asymmetrical.

Pulses may be applied in continuous or intermittent trains (i.e., thestimulus frequency changes as a function of time). In the case ofintermittent pulses, the on/off duty cycle of pulses may be symmetricalor asymmetrical, and the duty cycle may be regular and repeatable fromone intermittent burst to the next or the duty cycle of each set ofbursts may vary in a random (or pseudo random) fashion. Varying thestimulus frequency and/or duty cycle may assist in warding offhabituation because of the stimulus modulation.

The stimulating frequency may range from e.g., about 1 Hz to about 300Hz, and the frequency of stimulation may be constant or varying. In thecase of applying stimulation with varying frequencies, the frequenciesmay vary in a consistent and repeatable pattern or in a random (orpseudo random) fashion or a combination of repeatable and randompatterns.

In a representative embodiment, the stimulator is set to an intensity(e.g. 1-2 mA (or 0.1-40 mA, or 0.01-200 mA), 100-300 us (or 40-1000 us,or 1-10,000 us)) sufficient to activate the targeted nerve of passage atsome distance (e.g. 1 mm) away (from the targeted nerve of passage). Ifthe stimulus intensity is too great, it may generate muscle twitch(es)or contraction(s) sufficient to disrupt correct placement of the lead.If stimulus intensity is too low, the lead may be advanced too close tothe targeted nerve of passage (beyond the optimal position), possiblyleading to incorrect guidance, nerve damage, mechanically evokedsensation (e.g. pain and/or paresthesia) and/or muscle contraction (i.e.when the lead touches the nerve of passage), inability to activate thetarget nerve fiber(s) without activating non-target nerve fiber(s),improper placement, and/or improper anchoring of the lead (e.g. the leadmay be too close to the nerve and no longer able to anchor appropriatelyin the muscle tissue).

In a representative embodiment, the stimulator is set to a frequency(e.g. 0.5-12 Hz (or 0.1-20 Hz, or 0.05-40 Hz)) low enough to evokevisible muscle twitches (i.e. non-fused muscle contraction) and/ormuscle contraction(s) of the targeted muscle(s) innervated by the targetnerve of passage, but high enough that that the targeted nerve ofpassage will be activated before the lead is advanced beyond the optimalposition.

As an alternative to using muscle twitch(es) or contraction(s) asindicator(s) of lead placement (distance from the nerve of passage toelectrode contact), patient sensation could instead be used to indicatelead location relative to the targeted nerve of passage. Any combinationof stimulus parameters that evoke sensation(s) may be used. Somestimulus parameters may evoke a more desirable response (e.g. morecomfortable sensation, or a sensation that may be correlated with orspecific to the specific target nerve fiber(s) within the targeted nerveof passage. As an example, higher frequencies (e.g. 12 Hz, or 4 Hz, or0.1 Hz) may evoke sensation(s) or comfortable paresthesia(s) in theregion(s) of pain or in alternate target region(s) (real or phantom) andthough they may (or may not) also evoke muscle contraction(s), themuscle contraction(s) may not be noticeable (e.g. stimulus intensity maynot be sufficient to evoke a contraction or a twitch from the presentlead location or stimulus intensity may be sufficient to evokecontraction but the muscle contraction is fused (and no longer visuallytwitching), making it difficult to observe visually, unless EMG isused). To take advantage of both potential indicator responses (muscletwitch and patient sensation), higher frequencies may be appliedintermittently (at lower frequencies), where the higher frequencies(e.g. 20-120 Hz, or 12-200 Hz) would normally caused fused musclecontraction if they were applied continuously but they are applied at anintermittent frequency (e.g. 0.5-4 Hz, or 0.1-11 Hz) that is low enoughto allow the muscle to relax during the gaps between the bursts ofstimulation, making it easier to visualize while still generatingpatient sensation at a higher frequency, allowing both muscle twitch andpatient sensation to be used simultaneously as indicators of leadlocation relative to the targeted nerve of passage.

While stimulation is being applied, the lead (non-limiting examples ofthe lead could include a single or multi-contact electrode that isdesigned for temporary (percutaneous) or long-term (implant) use or aneedle electrode (used for in-office testing only)) may be advanced(e.g. slowly advanced) towards the targeted nerve of passage until thedesired indicator response (e.g. muscle twitch, muscle contraction,patient sensation, and/or some combination) is obtained. The intensitymay then be decreased (e.g. gradually decreased) as the lead is advanced(e.g. advanced slowly) closer to the targeted nerve of passage until thedesired indicator response(s) may be obtained at smaller intensity(ies)within the target range (e.g. 0.1-1.0 mA (or 0.09-39 mA, or 0.009-199mA), 100-300 us (or 40-1000 us, or 1-10,000 us)) at some distance (e.g.X2 mm, where X2<X1, and (as a non-limiting example) X1 may be multipletimes larger than X2, such as X1≧2*X2, or X1≧5*X2, or X1≧20*X2) from thetarget nerve. If specific response(s) (e.g. desired response(s) and/orundesired response(s)) can be obtained at a range of intensities thatare too low, then the lead may be located in a non-optimal location(e.g. too close to the target nerve(s)). Non-limiting examples of rangesof intensities that may be considered too low include those that are afraction (e.g. <⅔, or <⅕, or < 1/10) of the intensities that obtainedthe desired response(s) at X1.

The preferred stimulus intensities are a function of many variables, aremeant to serve as non-limiting examples only, and may need to be scaledaccordingly. As an example, if electrode shape, geometry, or surfacearea were to change, then the stimulus intensities may need to changeappropriately. For example, if the intensities were calculated for alead with an electrode surface area of approximately 20 mm², then theymay need to be scaled down accordingly to be used with a lead with anelectrode surface area of 0.2 mm² because a decrease in stimulatingsurface area may increase the current density, increasing the potentialto activate excitable tissue (e.g. target and non-target nerve(s) and/orfiber(s)). Alternatively, if the intensities were calculated for a leadwith an electrode surface area of approximately 0.2 mm², then theintensities may need to be scaled up accordingly to be used with a leadwith an electrode surface area of 20 mm². Alternatively, stimulusintensities may need to be scaled to account for variations in electrodeshape or geometry (between or among electrodes) to compensate for anyresulting variations in current density. In a non-limiting example, theelectrode contact surface area may be 0.1-20 mm², 0.01-40 mm², or0.001-200 mm². In a non-limiting example, the electrode contactconfiguration may include one or more of the following characteristics:cylindrical, conical, spherical, hemispherical, circular, triangular,trapezoidal, raised (or elevated), depressed (or recessed), flat, and/orborders and/or contours that are continuous, intermittent (orinterrupted), and/or undulating.

Stimulus intensities may need to be scaled to account for biologicalfactors, including but not limited to patient body size, weight, mass,habitus, age, and/or neurological condition(s). As a non-limitingexample, patients that are older, have a higher body-mass index (BMI),and/or neuropathy (e.g. due to diabetes) may need to have stimulusintensities scaled higher (or lower) accordingly (Bigeleisen et al2009).

As mentioned above, if the lead is too far away from the targeted nerveof passage, then stimulation may be unable to evoke the desired response(e.g. muscle contraction(s), comfortable sensation(s) (orparesthesia(s)), and/or pain relief) in the desired region(s) at thedesired stimulus intensity(ies). If the lead is too close to thetargeted nerve of passage, then stimulation may be unable to evoke thedesired response(s) (e.g. muscle contraction(s), comfortablesensation(s) (or paresthesia(s)), and/or pain relief) in the desiredregion(s) at the desired stimulus intensity(ies) without evokingundesirable response(s) (e.g. unwanted and/or painful musclecontraction(s), sensation(s) (or paresthesia(s)), increase in pain,and/or generation of additional pain in related or unrelated area(s)).In some cases, it may difficult to locate the optimal lead placement (ordistance from the targeted nerve of passage and/or it may be desirableto increase the range stimulus intensities that evoke the desiredresponse(s) without evoking the undesired response(s) so alternativestimulus waveforms and/or combinations of leads and/or electrodecontacts may be used. A non-limiting example of alternative stimuluswaveforms may include the use of a pre-pulse to increase theexcitability of the target fiber(s) and/or decrease the excitability ofthe non-target fiber(s).

Those skilled in the art will recognize that, for simplicity andclarity, the full structure and operation of all devices and processessuitable for use with the present invention is not being depicted ordescribed herein. Instead, only so much of an implantable pulsegenerator and supporting hardware as is unique to the present inventionor necessary for an understanding of the present invention is depictedand described. The remainder of the construction and operation of theIPGs described herein may conform to any of the various currentimplementations and practices known in the art.

VII. REPRESENTATIVE INDICATIONS FOR CHRONIC OR TEMPORARY PAIN THERAPY

Localized pain in any area of the body (e.g., the skin, bone, joint, ormuscle) can be treated with by applying electrical stimulation to amuscle in electrical contact with but spaced from a targeted nerve ofpassage. Electrical stimulation of nerves of passage works byinterfering with or blocking pain signals from reaching the brain, asFIG. 10 schematically shows.

Many pain indications can be treated by nerves of passage stimulation.

Pain in the leg may occur in areas such as the thigh, calf, hip, shin,knee, foot, ankle, and toes. There may be multiple causes of leg pain,including but not limited to injury (e.g. traumatic) to a muscle, joint,tendon, ligament or bone; muscle or ligament damage; ligament sprain,muscle or tendon strain; disease or disorders; phlebitis, swelling, orinflammation; claudication; insufficient blood flow into (arterialinsufficiency) or away from (venous insufficiency) a part of the leg orfoot; ischemia; peripheral artery disease; arthritis; tumor (malignantor benign); peripheral neuropathy; diabetic peripheral neuropathy; andpost herpetic neuralgia.

For example, peripheral artery disease can cause pain (especially duringactivity such as walking or running) because the effective narrowing ofthe arteries leads to a decrease in the supply of blood and therefore inthe supply of nutrients such as oxygen to the active muscles, leading topain. This phenomenon can occur in almost in area of the body but may bemore common in the leg, especially parts of the lower leg, such as thecalf. Activity is not always required to elicit pain and pain may occureven at rest (without activity or exercise). Nerve entrapment,compression, injury or other types of damage may cause pain in the areasinnervated by the damaged nerve, which can lead to referred pain in anarea distal to the injury.

The femoral nerve has anterior branches (intermediate cutaneous nerveand medial cutaneous nerve) and posterior branches. The saphenous nerve(branch of the femoral nerve) provides cutaneous (skin) sensation in themedial leg. Other branches of the femoral nerve innervate structures(such as muscles, joints, and other tissues) in the thigh and around thehip and knee joints. As an example, branches of the femoral nerveinnervate the hip joint, knee joint, and the four parts of theQuadriceps femoris (muscle): Rectus femoris (in the middle of the thigh)originates on the ilium and covers most of the other three quadricepsmuscles. Under (or deep to) the rectus femoris are the other 3 of thequadriceps muscles, which originate from the body of the femur. Vastuslateralis (on the outer side of the thigh) is on the lateral side of thefemur. Vastus medialis (on the inner part thigh) is on the medial sideof the femur. Vastus intermedius (on the top or front of the thigh) liesbetween vastus lateralis and vastus medialis on the front of the femur.Braches of the femoral nerve often innervate the pectineus and Sartoriusmuscles arises.

The sciatic nerve has branches that innervate the biceps femoris,semitendinosus, semimembranosus, and adductor magnus muscles. 2 majorbranches of the sciatic nerve are the tibial and common peroneal nervesthat innervate much of the lower leg (around and below the knee). Forexample, the tibial nerve innervates the gastrocnemius, popliteus,soleus and plantaris muscles and the knee joint. Most of the foot isinnervated by the tibial and peroneal nerve.

For example, claudication pain (occurring in the calf muscle) could betreated by nerves of passage stimulation by placing the lead in thegluteus muscle near the sciatic nerve, which passes by the gluteusmuscle on its way to innervate the calf muscle.

In general pain due to poor blood flow to an area or damage to an areacan be relieved by stimulation of the nerve innervating that area. Sincediabetic neuropathy typically leads to pain in the more distal areas(toes/foot), stimulation of the sciatic nerve can relive that pain. Painin the skin of the medial (inner) calf can be relieved by stimulation ofthe femoral nerve. Pain in the front of the thigh (quad's) can berelieved by stimulation of the femoral nerve. If pain overlaps more thanone area, stimulation of multiple nerves (e.g., sciatic and femoralnerves) can be beneficial.

Stimulation of the intercostal nerves (originating from the Thoracicnerve roots (T1-12)) can relieve pain in regions innervated by theintercostal nerves such as pain from intercostal neuralgia or postherpetic neuralgia. The pain may be confined to the area (e.g.dermatomic area) innervated by 1 or 2 nerves and may follow outbreak(and recovery) of herpes zoster. The pain may last up to several monthsor years in some patients and may be caused by nerve irritation ordamage due to herpes zoster.

Amputation (phantom) pain can also be treated by nerves of passagestimulation. For example, upper extremity stimulation of spinal nervespassing through the brachial plexus can relive phantom pain that resultsfrom amputation of an upper limb. Likewise, lower extremity stimulationof spinal nerves passing through the lumber plexus sacral plexus (e.g.,the sciatic nerve or the femoral nerve) can relive phantom pain thatresults from amputation of a lower limb.

VIII. CONCLUSION

In “nerves of passage” stimulation, the lead is placed in a muscle bywhich the targeted nerve passes, but stimulation actually relieves painthat is felt distal (downstream) from where the lead is placed. In“nerves of passage” stimulation, the lead can be placed in a muscle thatis conveniently located near a nerve trunk that passes by the lead onthe way to the painful area. The key is that the lead is placed in amuscle that is not the target (painful) muscle, but rather a muscle thatis proximal (upstream) from the painful region because the proximalmuscle is a more convenient and useful location to place the lead.

The advantages of nerves of passage stimulation can be recognized byanesthesiologists who are used to placing needles deeper in the musclenear nerves of passage Anesthesiologists are accustomed to placingneedles proximal (upstream) from the areas of pain to numb the areasdownstream. Anesthesiologists already use ultrasound and theelectro-location techniques that would be needed to place leads toaccess nerves of passage.

Nerves of passage stimulation provides stimulation-generatedparesthesias (that ideally overlap with the area of pain) but does notrequire evoking a muscle contraction to place the lead correctly. Thetarget regions in which pain is felt and which are targeted forgeneration of paresthesia are not the same region in which the lead isplaced. This is an advantage because physicians (e.g. anesthesiologists)who will typically be placing the lead are accustomed to usingparesthesias (sensory feedback description of from the patient) to guidelead placement and tuning of stimulation parameters.

Evoking muscle contraction with stimulation is not required for painrelief or lead location. Evoking muscle contraction with stimulation mayhelp in relieving pain or placing the lead, but it is not required. Itis an advantage that muscle contraction is not required because itallows this method to treat pains in which muscle contraction cannot beevoked (e.g. in the case of amputation pain in which the target area hasbeen amputated and is no longer physically present or other cases ofnerve damage either due to a degenerative diseases or conditions such asdiabetes of impaired vascular function, in which the nerves are slowlydegenerating, progressing from the periphery, or due to trauma.

In nerves of passage stimulation, the primary targeted pain area isdistal to the lead, meaning that the lead is in between the major areain which pain (e.g. the worst, most troubling, or most interfering pain)is felt and the center of the body (e.g. the spinal cord)).

Imaging (e.g., ultrasound or an alternate imaging technique, e.g.fluoroscopy) may be used to improve lead placement near nerves ofpassage. Ultrasound may improve lead placement in the form of increasingthe total speed of the procedure (shortening the procedure's duration,not necessarily increasing the speed at which the lead is advanced inthe form of locating the lead in a more optimal location (to improverecruitment of the target fibers in the target nerve and minimizerecruitment of non-target fibers (e.g. c fibers, other non-targetsensory fibers, motor fibers, etc.) in either the target nerve and/or innon-target nerve(s), in the form of minimizing risk and/or damage to thepatient during placement of the lead (by avoiding blood vessels, organs,bones, ligaments, tendons, lymphatic vessels, &/or other structures)that may be damaged. One reason that imaging may be useful is that somenerves of passage are (but do not have to be) located relatively deeply.Fluoroscopy is not required to place the lead. It may help, but it isnot required. Imaging is not required.

The patient is not required to give verbal, written, or other type offeedback or indication of what they feel as the lead is being advancedtowards the nerve of passage if muscle contraction or imaging is used toguide lead placement, but patient feedback during lead advancement mayimprove lead placement in some patients, especially in cases where(distal) muscle contraction cannot be used to confirm correct leadplacement (e.g. amputees, nerve injury, nerve degeneration (e.g. due tovascular dysfunction, diabetes, etc), stimulation of a sensory nerve).The patient may indicate sensations during tuning of stimulus intensity(but this is a different step in the process and is performed after thelead has been correctly positioned). As non-limiting examples, thosesensations reported by the patient may include first sensation (minimumstimulus intensity that evokes a sensation), level of comfort, maximumtolerable sensation, pain, qualities &/or descriptions of thesensations.

The region in which the patient perceives stimulation-induced sensationsand/or paresthesias may be an important indicator of the potentialsuccess of the therapy (e.g. used in screening potential candidates),and the stimulation parameters (including but not limited to leadlocation) may be adjusted so that the region in which paresthesias areperceived overlaps with the region of pain.

As an alternative to using perception of stimulation induced sensationsand/or paresthesia, the level of pain and/or change in the intensity ofpain during and/or due to stimulation may be used to adjust stimulationparameters (including but not limited to lead location).

The foregoing is considered as illustrative only of the principles ofthe invention. Furthermore, since numerous modifications and changeswill readily occur to those skilled in the art, it is not desired tolimit the invention to the exact construction and operation shown anddescribed. While the desired embodiment has been described, the detailsmay be changed without departing from the invention.

Various features of the invention are set forth in the following Claims.

1. A method to reduce and/or relieve pain in a painful regioncomprising: activating a peripheral nerve innervating the painful regionwith an electrode near the peripheral nerve and outside of the painfulregion; and evoking a tingling sensation over at least a portion of thepainful region without damaging the peripheral nerve.
 2. The method ofclaim 1, wherein the activation step is conducted a therapeutic time. 3.The method of claim 2, wherein at a conclusion of the therapeutic timethe electrode is removed
 4. The method of claim 2, wherein thetherapeutic time ranges from approximately one week to twelve weeks. 5.The method of claim 1, wherein pain relief is sustained after removal ofthe electrode.
 6. The method of claim 1, wherein the peripheral nerveincludes a peripheral nerve passing through at least one of a brachialplexus, lumbar plexus, sacral plexus, and cervical plexus.
 7. The methodof claim 1, wherein the peripheral nerve includes at least one of afemoral nerve, sciatic nerve, radial nerve, median nerve, ulnar nerve,and an intercostal nerve.
 8. A system to reduce and/or relieve pain in apainful region, the system comprising: an electrode placed near aperipheral nerve innervating the painful region and outside of thepainful region; and an electrical stimulator operatively coupled withthe electrode, the electrical stimulator evoking a tingling sensationover at least a portion of the painful region without damaging theperipheral nerve.
 9. The system of claim 8, wherein the electrode isinserted without surgery.
 10. The system of claim 8 further comprising alead operatively coupled with the electrode.
 11. The system of claim 10,wherein the lead is no greater than about 0.75 mm diameter.
 12. Thesystem of claim 10, wherein the lead is configured to withstandmechanical forces and resists migration during the evoking of thetingling sensation.
 13. The system of claim 10, wherein the leadincludes a coiled fine wire electrode lead.
 14. The system of claim 13,wherein the coiled fine-wire lead is configured to withstand mechanicalforces and resists migration during long-term use.
 15. The system ofclaim 10, wherein the lead includes one or more coiled metal wireswithin an open or flexible elastomer core.
 16. The system of claim 15,wherein the wire is insulated.
 17. The system of claim 16, wherein thewire is insulated with a biocompatible polymer film.
 18. The system ofclaim 17, wherein the biocompatible polymer film includes at least oneof polyfluorocarbon, polyimide, or parylene.
 19. The system of claim 10,wherein the lead is coated with a textured, bacteriostatic material. 20.A method to alleviate pain comprising: placing at least one electrodenear a peripheral nerve innervating a painful region, the at least oneelectrode positioned outside of the painful region; applying stimulationthrough the at least one electrode; and activating the peripheral nerveto alleviate pain in the painful region without functional nervestimulation at a motor point and without damaging the peripheral nerve.21. The method of claim 20 further comprising evoking a tinglingsensation over at least a portion of the painful region.
 22. The methodof claim 21, wherein evoking the tingling sensation includes applying anelectrical stimulation to the peripheral nerve during or after theinsertion of the at least one electrode and determining whether theelectrical stimulation of the peripheral nerve generates the tinglingsensation over the at least a portion of the targeted painful region.23. The method of claim 20, wherein placing the at least one electrodeis guided by a patient's report of the tingling sensation.
 24. Themethod of claim 23, wherein the patient's report of the tinglingsensation indicates confirmation of placement of the at least oneelectrode to alleviate the pain in the targeted painful region.
 25. Themethod of claim 20, wherein the placing of the at least one electrode isupstream of a joint of a patient and free of interference with thejoint.
 26. The method of claim 20, wherein the painful region includesan incision from surgery and the at least one electrode is placed remotefrom the incision.
 27. The method according to claim 20, wherein patientfeedback is not required to position the at least one electrode.
 28. Amethod to alleviate pain comprising: placing at least one electrodewithin at least one of a range of distances from a peripheral nerveinnervating a painful region, applying simulation through the at leastone electrode; and activating the peripheral nerve to alleviate pain inthe painful region without functional nerve stimulation at a motor pointand without damaging the peripheral nerve.
 29. A method to alleviatepain comprising: inserting a coiled lead into a patient; placing anelectrode coupled with the lead within a distance from a peripheralnerve innervating a painful region, applying simulation through the atleast one electrode, wherein intensity of the stimulation is related tothe distance; activating the peripheral nerve to alleviate pain in thepainful region without functional nerve stimulation at a motor point andwithout damaging the peripheral nerve.
 30. The method of claim 29,wherein the peripheral nerve includes a nerve trunk.
 31. The method ofclaim 30, wherein activating the nerve trunk alleviates the pain in thepainful region.
 32. The method according to claim 29, wherein the leadis inserted into tissue upstream of the targeted pain area.
 33. Themethod according to claim 29, wherein the electrode is placed remotefrom and upstream of the painful region.